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

HRID 450264Notes

Reaction equation

HRID 450264 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

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27563701-Boc-3-aminopyrrolidineHCID 46224264methanesulfonic acid 6-[1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-4-ylmethyl ester

Product 1

HCID 59394560(+/-)-3-({6-[1-(3-Trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-4-ylmethyl}-amino)-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

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

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

Sources & evidence

ORD record
ord-886e214340a44d59a4d2efb2de2fecfa
Source dataset
uspto-grants-2013_07
Patent number
US08486954B2

Reaction notes

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