Propiolic Acid → N-((1S,2R)-2-((6-(2-chloro-3-ethoxy-6-fluorophenyl)quinazolin-2-yl)amino)cyclopentyl)propiolamide

HRID 56362

Reaction equation

HRID 56362 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH2:9][CH3:10])=[CH:6][CH:5]=[C:4]([F:11])[C:3]=1[C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[N:18]=[C:17]([NH:22][C@@H:23]1[CH2:27][CH2:26][CH2:25][C@@H:24]1[NH2:28])[N:16]=[CH:15]2.[C:29](O)(=[O:32])[C:30]#[CH:31].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>[Cl:1][C:2]1[C:7]([O:8][CH2:9][CH3:10])=[CH:6][CH:5]=[C:4]([F:11])[C:3]=1[C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[N:18]=[C:17]([NH:22][C@@H:23]1[CH2:27][CH2:26][CH2:25][C@@H:24]1[NH:28][C:29](=[O:32])[C:30]#[CH:31])[N:16]=[CH:15]2

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 118036396(1R,2S)-N1-(6-(2-chloro-3-ethoxy-6-fluorophenyl)quinazolin-2-yl)cyclopentane-1,2-diamine

Product 1

HCID 118036276N-((1S,2R)-2-((6-(2-chloro-3-ethoxy-6-fluorophenyl)quinazolin-2-yl)amino)cyclopentyl)propiolamideYield 77.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (1R,2S)—N1-(6-(2-chloro-3-ethoxy-6-fluorophenyl)quinazolin-2-yl)cyclopentane-1,2-diamine (0.1 mmol), propiolic acid (0.007 mL, 0.12 mmol), HATU (57 mg, 0.15 mmol) and DIEA (0.052 mL, 0.3 mmol) in dichloromethane (1 mL) was stirred at room temperature for 40 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-chloro-3-ethoxy-6-fluorophenyl)quinazolin-2-yl)amino)cyclopentyl)propiolamide (Compound 6) (35 mg, 76%). MS (ES+) C24H22ClFN4O2 requires: 452, found: 453 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-f5e08186e6d84a5c97e5ea61c17dc160
Source dataset
uspto-grants-2016_09
Patent number
US09434700B2

Linked notes

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