Oxalyl chloride → N-(4-(tert-Butylamino)quinazolin-8-yl)-6-chloro-2-fluoro-3-((3-hydroxy-2,2-dimethylpropanamido)methyl)benzamide

HRID 1469855Notes

Reaction equation

HRID 1469855 reaction equation
[C:1]([NH:5][C:6]1[C:15]2[C:10](=[C:11]([NH2:16])[CH:12]=[CH:13][CH:14]=2)[N:9]=[CH:8][N:7]=1)([CH3:4])([CH3:3])[CH3:2].[Cl:17][C:18]1[C:23]([C:24](O)=[O:25])=[C:22]([F:27])[C:21]([CH2:28][NH:29][C:30](=[O:36])[C:31]([CH3:35])([CH3:34])[CH2:32][OH:33])=[CH:20][CH:19]=1.C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[C:1]([NH:5][C:6]1[C:15]2[C:10](=[C:11]([NH:16][C:24](=[O:25])[C:23]3[C:18]([Cl:17])=[CH:19][CH:20]=[C:21]([CH2:28][NH:29][C:30](=[O:36])[C:31]([CH3:35])([CH3:34])[CH2:32][OH:33])[C:22]=3[F:27])[CH:12]=[CH:13][CH:14]=2)[N:9]=[CH:8][N:7]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 866922636-Chloro-2-fluoro-3-((3-hydroxy-2,2-dimethylpropanamido)methyl)benzoic acidHCID 86692301N4-(tert-butyl)quinazoline-4,8-diamine

Product 1

HCID 71680056N-(4-(tert-Butylamino)quinazolin-8-yl)-6-chloro-2-fluoro-3-((3-hydroxy-2,2-dimethylpropanamido)methyl)benzamideYield 10.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared following the procedure described in Example-1 using N4-(tert-butyl)quinazoline-4,8-diamine (Intermediate-55, 100 mg, 0.46 mmol), 6-chloro-2-fluoro-3-((3-hydroxy-2,2-dimethylpropanamido)methyl)benzoic acid (Intermediate-59, 168 mg, 0.56 mmol), oxalyl chloride (116 mg, 0.92 mmol), DMF (1 drop) and DIPEA (178 mg, 1.37 mmol) in CH2Cl2 (2 mL) to afford 25 mg of the title product. 1H NMR (300 MHz, DMSO-d6): δ 10.41 (s, 1H), 8.68 (d, J=7.8 Hz, 1H), 8.51 (s, 1H), 8.17 (d, J=8.1 Hz, 1H), 8.11 (t, 1H), 7.52-7.38 (m, 4H), 4.91 (t, 1H), 4.33 (d, J=6.3 Hz, 2H), 3.42 (d, 2H), 1.55 (s, 9H), 1.08 (s, 6H); MS [M+H]+: 502.46.

Workup

  1. customThe title compound was prepared

Sources & evidence

ORD record
ord-ea55583471834e1ca3ac205df8bc6e2f
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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