Diisopropylethylamine → (+/-)-3-({6-[1-(3-Trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-4-ylmethyl}-amino)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 45117

Reaction equation

[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([NH:9][C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][C:22]4[N:27]=[CH:26][N:25]=[C:24]([CH2:28]OS(C)(=O)=O)[CH:23]=4)=[CH:18][CH:19]=3)[CH:14]=[CH:13]2)=[O:11])[CH:6]=[CH:7][CH:8]=1.[C:36]([O:40][C:41]([N:43]1[CH2:47][CH2:46][CH:45]([NH2:48])[CH2:44]1)=[O:42])([CH3:39])([CH3:38])[CH3:37].C(N(C(C)C)CC)(C)C>C1COCC1.CCOC(C)=O>[C:36]([O:40][C:41]([N:43]1[CH2:47][CH2:46][CH:45]([NH:48][CH2:28][C:24]2[CH:23]=[C:22]([O:21][C:17]3[CH:16]=[C:15]4[C:20](=[CH:19][CH:18]=3)[N:12]([C:10](=[O:11])[NH:9][C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:35])([F:34])[F:1])[CH:4]=3)[CH:13]=[CH:14]4)[N:27]=[CH:26][N:25]=2)[CH2:44]1)=[O:42])([CH3:39])([CH3:37])[CH3:38]

Participants

Conditions

Temperature: 60 °C

Procedure

To the solution of methanesulfonic acid (±)-6-[1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-4-ylmethyl ester (80 mg, 0.158 mmol) in THF (5 mL), 3-amino-pyrrolidine-1-carboxylic acid tert-butyl ester (88 mg, 0.474 mmol) and diisopropylethylamine (61 mg, 0.474 mmol) are added. The resulting solution is stirred at 60° C. overnight. After cooling to rt, the reaction mixture is diluted with EtOAc and washed with water and then brine. The organic layer is dried with anhydrous Na2SO4, filtered, and condensed. The residue is purified by FCC (0-10% MeOH/DCM) to provide the title compound. MS (ESI) m/z 597.2 (M+1).

Workup

temperatureAfter cooling to rt
washwashed with water
dry with materialThe organic layer is dried with anhydrous Na2SO4
filtrationfiltered
customcondensed
customThe residue is purified by FCC (0-10% MeOH/DCM)

Sources & evidence

ORD record: ord-e85091ad253448118ee39a8dae6825ca
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08541432B2

Linked notes

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