Oxalyl chloride → 6-Chloro-2-fluoro-N-(7-methyl-4-((3-(trifluoromethyl)phenyl)amino)quinazolin-8-yl)-3-(pivalamidomethyl)benzamide

HRID 1469831Notes

Reaction equation

HRID 1469831 reaction equation
[CH3:1][C:2]1[C:11]([NH2:12])=[C:10]2[C:5]([C:6]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=3)=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.[Cl:24][C:25]1[C:30]([C:31](O)=[O:32])=[C:29]([F:34])[C:28]([CH2:35][NH:36][C:37](=[O:42])[C:38]([CH3:41])([CH3:40])[CH3:39])=[CH:27][CH:26]=1.C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[Cl:24][C:25]1[C:30]([C:31]([NH:12][C:11]2[C:2]([CH3:1])=[CH:3][CH:4]=[C:5]3[C:10]=2[N:9]=[CH:8][N:7]=[C:6]3[NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:21])[F:22])[CH:15]=2)=[O:32])=[C:29]([F:34])[C:28]([CH2:35][NH:36][C:37](=[O:42])[C:38]([CH3:40])([CH3:39])[CH3:41])=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 584833746-Chloro-2-fluoro-3-(pivalamidomethyl)benzoic acidHCID 673386327-methyl-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine

Product 1

HCID 716793926-Chloro-2-fluoro-N-(7-methyl-4-((3-(trifluoromethyl)phenyl)amino)quinazolin-8-yl)-3-(pivalamidomethyl)benzamideYield 9.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared following the procedure described in Example-1 using 7-methyl-N4-(3-(trifluoromethyl)phenyl)quinazoline-4,8-diamine (Intermediate-37, 140 mg, 0.44 mmol), 6-chloro-2-fluoro-3-(pivalamidomethyl)benzoic acid (Intermediate-2, 163 mg, 0.57 mmol), oxalyl chloride (108 mg, 0.86 mmol), DMF (1 drop) and DIPEA (170 mg, 1.32 mmol) in CH2Cl2 (5 mL) to afford 25 mg of the title product. 1H NMR (300 MHz, DMSO-d6): δ 10.71 (s, 1H), 10.03 (s, 1H), 8.72 (s, 1H), 8.46 (d, J=8.4 Hz, 1H), 8.35 (s, 1H), 8.27 (d, J=9.3 Hz, 1H), 8.19 (t, 1H), 7.66-7.63 (m, 2H), 7.46 (d, J=6.9 Hz, 1H), 7.40 (d, J=8.7 Hz, 1H), 7.31 (t, J=8.1 Hz, 1H), 4.33 (d, J=5.4 Hz, 2H), 2.50 (s, 3H), 1.15 (s, 9H); MS (m/z): 588.23 (M)+.

Workup

  1. customThe title compound was prepared

Sources & evidence

ORD record
ord-567e223c8dc64a7ab38b33c6e5405328
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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