Cyclopropylamine → tert-butyl ((1S,2R)-2-((6-(4-(cyclopropylcarbamoyl)-2-methoxyphenyl)quinazolin-2-yl)amino)cyclopentyl)carbamate

HRID 56365Notes

Reaction equation

HRID 56365 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][CH2:11][C@H:10]1[NH:14][C:15]1[N:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[C:20]([C:25]3[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][C:26]=3[O:34][CH3:35])[CH:21]=2)[N:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:36]1([NH2:39])[CH2:38][CH2:37]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>ClCCl>[CH:36]1([NH:39][C:29]([C:28]2[CH:32]=[CH:33][C:25]([C:20]3[CH:21]=[C:22]4[C:17](=[CH:18][CH:19]=3)[N:16]=[C:15]([NH:14][C@@H:10]3[CH2:11][CH2:12][CH2:13][C@@H:9]3[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])[N:24]=[CH:23]4)=[C:26]([O:34][CH3:35])[CH:27]=2)=[O:30])[CH2:38][CH2:37]1

Participants

6

Reactant 4

HCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118036549HCID 118036549, compound

Product 1

HCID 131736913tert-butyl ((1S,2R)-2-((6-(4-(cyclopropylcarbamoyl)-2-methoxyphenyl)quinazolin-2-yl)amino)cyclopentyl)carbamateYield 93.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-(2-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclopentyl)amino)quinazolin-6-yl)-3-methoxybenzoic acid (57 mg, 0.12 mmol), cyclopropyl amine (0.012 mL, 0.18 mmol), HATU (68 mg, 0.18 mmol) and DIEA (0.052 mL, 0.30 mmol) in dichloromethane (1.5 mL) was stirred at room temperature for 30 minutes. LC-MS indicated complete consumption of SM. The reaction mixture was purified by silica gel chromatography to yield tert-butyl ((1S,2R)-2-((6-(4-(cyclopropylcarbamoyl)-2-methoxyphenyl)quinazolin-2-yl)amino)cyclopentyl)carbamate (58 mg, 93%). MS (ES+) C29H35N5O4 requires: 517, found: 518 [M+H]+.

Workup

  1. customconsumption of SM
  2. customThe reaction mixture was purified by silica gel chromatography

Sources & evidence

ORD record
ord-a72523985bfa4767a91a3e050edf658e
Source dataset
uspto-grants-2016_09
Patent number
US09434700B2

Reaction notes

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