Oxalyl chloride → 6-Chloro-2-fluoro-3-((3-hydroxy-2,2-dimethylpropanamido)methyl)-N-(4-(3-(trifluoromethyl)phenoxy)quinazolin-8-yl)benzamide

HRID 1469852Notes

Reaction equation

HRID 1469852 reaction equation
[F:1][C:2]([F:22])([F:21])[C:3]1[CH:4]=[C:5]([CH:18]=[CH:19][CH:20]=1)[O:6][C:7]1[C:16]2[C:11](=[C:12]([NH2:17])[CH:13]=[CH:14][CH:15]=2)[N:10]=[CH:9][N:8]=1.[Cl:23][C:24]1[C:29]([C:30](O)=[O:31])=[C:28]([F:33])[C:27]([CH2:34][NH:35][C:36](=[O:42])[C:37]([CH3:41])([CH3:40])[CH2:38][OH:39])=[CH:26][CH:25]=1.C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[Cl:23][C:24]1[C:29]([C:30]([NH:17][C:12]2[CH:13]=[CH:14][CH:15]=[C:16]3[C:11]=2[N:10]=[CH:9][N:8]=[C:7]3[O:6][C:5]2[CH:18]=[CH:19][CH:20]=[C:3]([C:2]([F:1])([F:21])[F:22])[CH:4]=2)=[O:31])=[C:28]([F:33])[C:27]([CH2:34][NH:35][C:36](=[O:42])[C:37]([CH3:40])([CH3:41])[CH2:38][OH:39])=[CH:26][CH:25]=1

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 716803914-(3-(Trifluoromethyl)phenoxy)quinazolin-8-amineHCID 866922636-Chloro-2-fluoro-3-((3-hydroxy-2,2-dimethylpropanamido)methyl)benzoic acid

Product 1

HCID 866923056-Chloro-2-fluoro-3-((3-hydroxy-2,2-dimethylpropanamido)methyl)-N-(4-(3-(trifluoromethyl)phenoxy)quinazolin-8-yl)benzamideYield 2.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared following the procedure described in Example-1 using 4-(3-(trifluoromethyl)phenoxy)quinazolin-8-amine (Intermediate-8, 200 mg, 0.655 mmol), 6-chloro-2-fluoro-3-((3-hydroxy-2,2-dimethylpropanamido)methyl)benzoic acid (Intermediate-59, 237 mg, 0.78 mmol), oxalyl chloride (166 mg, 1.32 mmol), DMF (1 drop) and DIPEA (253 mg, 1.96 mmol) in CH2Cl2 (3 mL) to afford 10 mg of the title product. 1H NMR (300 MHz, DMSO-d6): δ 10.94 (s, 1H), 8.88 (d, 1H), 8.77 (s, 1H), 8.14 (m, 2H), 7.85 (m, 2H), 7.73 (s, 3H), 7.36 (m, 2H), 4.91 (t, 1H), 4.31 (d, 2H), 3.40 (m, 2H), 1.06 (s, 6H); MS [M+H]+: 591.29.

Workup

  1. customThe title compound was prepared

Sources & evidence

ORD record
ord-4226b5b881214f60b0ca0d669d459825
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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