Diisopropylethylamine → 9-[(R)-6-(2-chloro-4-fluoro-phenyl)-5-methoxycarbonyl-2-thiazol-2-yl-3,6-dihydro-pyrimidin-4-ylmethyl]-3-oxa-7,9-diaza-bicyclo[3.3.1]nonane-7-carboxylic acid tert-butyl ester

HRID 1778470Notes

Reaction equation

HRID 1778470 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH:14]2[NH:16][CH:10]([CH2:11][O:12][CH2:13]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[CH3:26][O:27][C:28]([C:30]1[C@H:31]([C:43]2[CH:48]=[CH:47][C:46]([F:49])=[CH:45][C:44]=2[Cl:50])[N:32]=[C:33]([C:38]2[S:39][CH:40]=[CH:41][N:42]=2)[NH:34][C:35]=1[CH2:36]Br)=[O:29]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]2[N:16]([CH2:36][C:35]3[NH:34][C:33]([C:38]4[S:39][CH:40]=[CH:41][N:42]=4)=[N:32][C@@H:31]([C:43]4[CH:48]=[CH:47][C:46]([F:49])=[CH:45][C:44]=4[Cl:50])[C:30]=3[C:28]([O:27][CH3:26])=[O:29])[CH:14]([CH2:13][O:12][CH2:11]2)[CH2:15]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 53415349tert-Butyl 3-oxa-7,9-diazabicyclo(3.3.1)nonane-7-carboxylateHCID 89995948Methyl (R)-6-(bromomethyl)-4-(2-chloro-4-fluorophenyl)-2-(thiazol-2-yl)-1,4-dihydropyrimidine-5-carboxylate

Product 1

HCID 1176974139-[(R)-6-(2-chloro-4-fluoro-phenyl)-5-methoxycarbonyl-2-thiazol-2-yl-3,6-dihydro-pyrimidin-4-ylmethyl]-3-oxa-7,9-diaza-bicyclo[3.3.1]nonane-7-carboxylic acid tert-butyl esterYield 94.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3-oxa-7,9-diaza-bicyclo[3.3.1]nonane-7-carboxylic acid tert-butyl ester (171 mg, 0.75 mmol) and DIPEA (0.45 mL, 2.5 mmol) in CH2Cl2 (10 mL) was added (R)-6-bromomethyl-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester (222 mg, 0.5 mmol). The mixture was stirred at room temperature for 16 hours. The mixture was concentrated in vacuo. The residue was purified by flash column chromatography to afford 9-[(R)-6-(2-chloro-4-fluoro-phenyl)-5-methoxycarbonyl-2-thiazol-2-yl-3,6-dihydro-pyrimidin-4-ylmethyl]-3-oxa-7,9-diaza-bicyclo[3.3.1]nonane-7-carboxylic acid tert-butyl ester as yellow oil (0.28 g, 94%). MS: calc'd (MH+) 592, measured (MH+) 592.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-b2ff703930a14b0cbcd1b17a04d90f77
Source dataset
uspto-grants-2016_02
Patent number
US09266904B2

Reaction notes

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