MINNEAPOLIS — A second straight road game had the favored 49ers desperately in need of a fourth-quarter comeback. This one failed, too.

The 49ers’ defense was in retreat throughout Monday night’s 22-17 loss to the Vikings, but it wasn’t until Brock Purdy had two passes intercepted in the final 5 1/2 minutes to seal a second straight defeat.

It was Purdy’s first career game with two interceptions, and they came on targets to Jauan Jennings and Ray-Ray McCloud, the receivers summoned to help fill in for Deebo Samuel, who is out with a shoulder he fractured in the previous week’s loss at Cleveland.

The 49ers (5-2) saw their defense repeatedly blow assignments and yield 378 passing yards to Kirk Cousins, who was not sacked and did not even have the services of star receiver Justin Jefferson (injured reserve). The Vikings (3-4) have won seven straight home games against the 49ers dating back to 1994.

If one play could define the 49ers’ defensive breakdowns, it was Jordan Addison’s 60-yard touchdown reception seven seconds before halftime. Charvarius Ward attempted to intercept Cousins’ pass like he did on the game’s opening series, but once Addison snatched the ball at the 35, there was no safety to stop him from scoring. That’s because defensive coordinator Steve Wilks’ third-and-6 blitz call backfired, and safety Tashaun Gipson Sr. was caught biting up on the play.

Asked if he was OK with the blitz call, 49ers coach Kyle Shanahan said: “That’s something we’ll discuss throughout this week. Obviously I did not like the result.”

Anger oozed afterward from 49ers’ leaders, both in the locker room and at the media podium.

“You just have to let the anger fuel you in the right ways and be obsessed with execution and doing your job,” running back Christian McCaffrey. “We have the right guys for that mentality. This isn’t a team that’s going to start folding.”

“The NFL will humble you every step of the way,” said defensive end Nick Bosa. “And getting off to a 5-0 start, you kind of get that confidence that we are who we need to be. But the NFL does that. It’s good players, good schemes, and we’re going to face another good team this week, so we’ve got to be ready.”

Next up is a Sunday home game against the Cincinnati Bengals (3-3). The Bengals are coming off their bye, just as the Cleveland Browns were before handing the 49ers their first defeat. The 49ers’ bye comes in Week 9, and while they remain atop the NFC West, it’s by a half-game over the Seattle Seahawks (4-2).

Purdy and the 49ers offense had chances to rectify their defense’s glaring woes in Monday’s waning moments.

Purdy converted a fourth-and-1 dive at midfield before throwing his first interception. Safety Camryn Bynum easily snared it at the Vikings’ 30-yard line, with Jennings trailing about 5 yards late on the route. Purdy and coach Kyle Shanahan both blamed the pass (“Bad ball,” Purdy said) and Jennings’ route, in which he stuttered a beat before cutting inside.

When the Vikings’ Greg Joseph missed a 50-yard field goal attempt with 1:11 remaining, it gave Purdy and the 49ers a final chance. After back-to-back completions to McCloud, the 49ers were at the Vikings’ 40-yard line. Purdy tried to hit McCloud again, only his pass found Bynum, again. “I could have ran and got down, but I forced it,” Purdy said.

“Their defense took three and we took one,” safety Talanoa Hufanga said of the turnover battle. “With those numbers, you’re going to lose.”

The Vikings were 7-of-10 on third-down conversions before a fourth-quarter stop forced them to punt for the first time, with 9:22 remaining.

McCaffrey, playing through an oblique injury, scored both 49ers’ touchdowns, extending his streak of 16 consecutive games with at least one score (one shy of Lenny Moore’s record with the 1965 Baltimore Colts).

The 49ers’ comeback bid caught fire when McCaffrey scored on a 35-yard catch-and-run down the right sideline, cutting the Vikings’ lead to 19-14 with 5:54 until the fourth quarter. Jennings and Brandon Aiyuk made key blocks to spring McCaffrey untouched the final 25 yards.

Aiyuk had five catches on five targets for 57 yards in the first half, then was thrown to only once after that, because Purdy said the Vikings’ zone defense essentially double-covered Aiyuk and forced Purdy to focus on the other half of the field.

Preceding that score were completions to McCaffrey (12 yards) and George Kittle (28), but before those plays, the 49ers’ mostly maligned defense came through with a goal-line stand, forcing the Vikings to settle for a 20-yard field goal. Another Vikings field goal, from 54 yards, pushed their lead to 22-14 only 20 seconds before the fourth quarter.

Jake Moody’s career-long 55-yard field goal pulled the 49ers within 22-17 with 13:21 to go. The rookie kicker had missed a 40-yard, second-quarter attempt wide right, which was eerily similar to a 41-yard, wide-right miss in the final seconds of last game’s 19-17 loss at Cleveland.

The 49ers, whose defense allowed a league-low 14.5 points per game through Week 6, had yielded 16 by halftime Monday night. Miscues had them in retreat. Ward had cleared out his locker and left before speaking to reporters, as was the case a week earlier when Gipson skipped out rather than discuss his unnecessary roughness penalty that sparked the Browns’ winning drive.

The 49ers had pulled within 10-7 with 1:01 until halftime, delivering a steady touchdown drive that was capped by a 3-yard scoring run from McCaffrey. That drive stayed alive by virtue of Aiyuk’s 25-yard, third-down catch at midfield, followed by a pair of third-and-1 conversion runs from McCaffrey, who scored behind blocks from Aaron Banks and Jaylon Moore, the latter of whom started in place of the injured Trent Williams.

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Each team committed a turnover on its opening possession — a Ward interception near midfield was followed by a McCaffrey fumble at the Vikings’ 12-yard line. The Vikings converted McCaffrey’s opening-drive fumble into a touchdown drive, with Cousins’ third-and-2 scoring strike sailing 20 yards to Jordan Addison; Dre Greenlaw trailed in coverage, Gipson Sr. was late to help, and Bosa jumped in vain to try blocking the ball at the line rather than rush the pocket.

One of the defense’s ugliest series this season came in the second quarter. It saw Fred Warner miss a tackle on a 13-yard run by Cam Akers, followed up with Cousins dropping a third-and-10 screen pass over two blitzing defenders, Greenlaw and Gipson, for a 30-yard catch-and-run by Akers to the 2-yard line. The Vikings settled for a 21-yard field goal on 10-0.

The 49ers defense made a successful goal-line stand after Deommodore Lenoir’s pass-interference penalty in the end zone, and the Vikings settled for a 20-yard field goal and 19-7 lead midway through the third quarter.

“We’ve shown obviously what we’re capable of, like our best version of ourselves,” Warner said. “But at the end of the day, I want our mental toughness to go up. I want to win in any form or fashion. I don’t care if it’s ugly, like all right, we’ll figure it out later on, but let’s find a way to get this done.”