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Propiolic Acid → N-((1S,2R)-2-((6-(2,6-difluoro-3-methoxyphenyl)quinazolin-2-yl)amino)cyclopentyl)propiolamide

HRID 56358
Notes
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Reaction equation

HRID 56358 reaction equation
[F:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[C:4]([F:10])[C:3]=1[C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[C:16]([NH:21][C@@H:22]1[CH2:26][CH2:25][CH2:24][C@@H:23]1[NH2:27])[N:15]=[CH:14]2.[C:28](O)(=[O:31])[C:29]#[CH:30].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>[F:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[C:4]([F:10])[C:3]=1[C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[C:16]([NH:21][C@@H:22]1[CH2:26][CH2:25][CH2:24][C@@H:23]1[NH:27][C:28](=[O:31])[C:29]#[CH:30])[N:15]=[CH:14]2
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 10110Propiolic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 118036498(1R,2S)-N1-(6-(2,6-difluoro-3-methoxyphenyl)quinazolin-2-yl)cyclopentane-1,2-diamine

Product 1

HCID 118036434
N-((1S,2R)-2-((6-(2,6-difluoro-3-methoxyphenyl)quinazolin-2-yl)amino)cyclopentyl)propiolamide
Yield 68.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (1R,2S)—N1-(6-(2,6-difluoro-3-methoxyphenyl)quinazolin-2-yl)cyclopentane-1,2-diamine (0.045 mmol), propiolic acid (0.004 mL, 0.067 mmol), HATU (25 mg, 0.067 mmol) and DIEA (0.023 mL, 0.135 mmol) in dichloromethane (1 mL) was stirred at room temperature for 60 minutes. LC-MS indicated complete consumption of SM. The reaction mixture was purified by silica gel chromatography to yield N-((1S,2R)-2-((6-(2,6-difluoro-3-methoxyphenyl)quinazolin-2-yl)amino)cyclopentyl)propiolamide (Compound 2) (13 mg, 68%). MS (ES+) C27H27N5O3 requires: 422, found: 423 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-64ce9dd073784f8788a478b58b3d9617
Source dataset
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09434700B2

Reaction notes

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