Diisopropylethylamine → (1R,5S)-8-[[(4R)-4-(2-chloro-4-fluoro-phenyl)-5-methoxycarbonyl-2-thiazol-2-yl-1,4-dihydropyrimidin-6-yl]methyl]-3-oxa-8-azabicyclo[3.2.1]octane-5-carboxylic acid

HRID 1778496Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[C@H:6]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=2[Cl:25])[N:7]=[C:8]([C:13]2[S:14][CH:15]=[CH:16][N:17]=2)[NH:9][C:10]=1[CH2:11]Br)=[O:4].[CH:26]12[NH:33][C:30]([C:34]([OH:36])=[O:35])([CH2:31][CH2:32]1)[CH2:29][O:28][CH2:27]2.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:25][C:19]1[CH:20]=[C:21]([F:24])[CH:22]=[CH:23][C:18]=1[C@H:6]1[C:5]([C:3]([O:2][CH3:1])=[O:4])=[C:10]([CH2:11][N:33]2[C@@:30]3([C:34]([OH:36])=[O:35])[CH2:31][CH2:32][C@@H:26]2[CH2:27][O:28][CH2:29]3)[NH:9][C:8]([C:13]2[S:14][CH:15]=[CH:16][N:17]=2)=[N:7]1

Participants

Conditions

Temperature: 25 °C

Procedure

A mixture of methyl (4R)-6-(bromomethyl)-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dihydropyrimidine-5-carboxylate (compound C, 61 mg, 0.138 mmol), 3-oxa-8-azabicyclo[3.2.1]octane-5-carboxylic acid 81a (20 mg, 0.127 mmol) and DIPEA (0.07 mL, 0.4 mmol) in DCM (5 mL) was stirred at 25° C. for 16 h. Then the mixture was concentrated in vacuo. The residue was purified by preparative HPLC to afford a pair of diastereomers, Example 81 and Example 82.

Workup

concentrationThen the mixture was concentrated in vacuo
customThe residue was purified by preparative HPLC
customto afford a pair of diastereomers, Example 81 and Example 82

Sources & evidence

ORD record: ord-a64b12277a934718a1c91a9ec3b4e63b
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266904B2

Reaction notes

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