2-(3-Oxa-8-azabicyclo[3.2.1]octan-6-yl)acetic acid → 2-[(1R,5S,6S)-8-[[(4R)-4-(2-bromo-4-fluoro-phenyl)-5-methoxycarbonyl-2-thiazol-2-yl-1,4-dihydropyrimidin-6-yl]methyl]-3-oxa-8-azabicyclo[3.2.1]octan-6-yl]acetic acid

HRID 1778491Notes

Reaction equation

HRID 1778491 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@H:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13]([CH2:19]Br)[NH:12][C:11]([C:21]2[S:22][CH:23]=[CH:24][N:25]=2)=[N:10]1.[CH:26]12[NH:37][CH:30]([CH:31]([CH2:33][C:34]([OH:36])=[O:35])[CH2:32]1)[CH2:29][O:28][CH2:27]2>>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@H:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13]([CH2:19][N:37]2[C@H:30]3[C@H:31]([CH2:33][C:34]([OH:36])=[O:35])[CH2:32][C@@H:26]2[CH2:27][O:28][CH2:29]3)[NH:12][C:11]([C:21]2[S:22][CH:23]=[CH:24][N:25]=2)=[N:10]1

Participants

3

Reactant 2

HCID 1176978292-(3-Oxa-8-azabicyclo[3.2.1]octan-6-yl)acetic acidHCID 117706695(R)-methyl 4-(2-bromo-4-fluorophenyl)-6-(bromomethyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate

Product 1

HCID 1177002202-[(1R,5S,6S)-8-[[(4R)-4-(2-bromo-4-fluoro-phenyl)-5-methoxycarbonyl-2-thiazol-2-yl-1,4-dihydropyrimidin-6-yl]methyl]-3-oxa-8-azabicyclo[3.2.1]octan-6-yl]acetic acidYield 24.2%

Procedure

The title compound was prepared in analogy to compound 1a in Example 1 starting from methyl (4R)-4-(2-bromo-4-fluoro-phenyl)-6-(bromomethyl)-2-thiazol-2-yl-1,4-dihydropyrimidine-5-carboxylate 53a (73 mg, 0.15 mmol) and 2-(3-oxa-8-azabicyclo[3.2.1]octan-6-yl)acetic acid (121 mg, 0.7 mmol) 64c. 21 mg of the title compound was isolated by preparative HPLC as a yellow powder (yield was 16%).

Sources & evidence

ORD record
ord-78e9458b48c8456087cec19c1121bf04
Source dataset
uspto-grants-2016_02
Patent number
US09266904B2

Reaction notes

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