Oxalyl chloride → tert-Butyl 4-chloro-2-fluoro-3-((4-((3-(trifluoromethyl)phenyl)amino)quinazolin-8-yl)carbamoyl)benzylcarbamate

HRID 1469745Notes

Reaction equation

HRID 1469745 reaction equation
[F:1][C:2]([F:22])([F:21])[C:3]1[CH:4]=[C:5]([NH:9][C:10]2[C:19]3[C:14](=[C:15]([NH2:20])[CH:16]=[CH:17][CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1.[C:23]([O:27][C:28]([NH:30][CH2:31][C:32]1[C:33]([F:42])=[C:34]([C:38]([Cl:41])=[CH:39][CH:40]=1)[C:35](O)=[O:36])=[O:29])([CH3:26])([CH3:25])[CH3:24].C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[Cl:41][C:38]1[CH:39]=[CH:40][C:32]([CH2:31][NH:30][C:28](=[O:29])[O:27][C:23]([CH3:26])([CH3:25])[CH3:24])=[C:33]([F:42])[C:34]=1[C:35](=[O:36])[NH:20][C:15]1[CH:16]=[CH:17][CH:18]=[C:19]2[C:14]=1[N:13]=[CH:12][N:11]=[C:10]2[NH:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:21])[F:22])[CH:4]=1

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 71680392HCID 71680392, compoundHCID 866922393-(((Tert-butoxycarbonyl)amino)methyl)-6-chloro-2-fluorobenzoic acid

Product 1

HCID 71677886tert-Butyl 4-chloro-2-fluoro-3-((4-((3-(trifluoromethyl)phenyl)amino)quinazolin-8-yl)carbamoyl)benzylcarbamateYield 47.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared following the procedure described in Example-1 using N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine (Intermediate-7, 87 mg, 0.285 mmol), 3-(((tert-butoxycarbonyl)amino)methyl)-6-chloro-2-fluorobenzoic acid (130 mg, 0.428 mmol), oxalyl chloride (81 mg, 0.64 mmol), DMF (1 drop) and DIPEA (111 mg, 0.86 mmol) in CH2Cl2 (4 mL) to afford 80 mg of the title product. 1H NMR (300 MHz, DMSO-d6): δ 10.66 (s, 1H), 10.14 (s, 1H), 8.82 (d, 1H), 8.71 (s, 1H), 8.36 (m, 2H), 8.23 (d, 1H), 7.73 (t, 1H), 7.66 (t, 1H), 7.51 (m, 2H), 7.42 (m, 2H), 4.18 (d, 2H), 1.40 (s, 9H); MS [M+H]+: 590.08.

Workup

  1. customThe title compound was prepared

Sources & evidence

ORD record
ord-895f886fb2624cb99a54855898c75baa
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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