Oxalyl chloride → 6-Chloro-N-(4-((4,4-difluorocyclohexyl)amino)quinazolin-8-yl)-2-fluoro-3-(pivalamidomethyl)benzamide

HRID 1469815Notes

Reaction equation

HRID 1469815 reaction equation
[F:1][C:2]1([F:20])[CH2:7][CH2:6][CH:5]([NH:8][C:9]2[C:18]3[C:13](=[C:14]([NH2:19])[CH:15]=[CH:16][CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH2:4][CH2:3]1.[Cl:21][C:22]1[C:27]([C:28](O)=[O:29])=[C:26]([F:31])[C:25]([CH2:32][NH:33][C:34](=[O:39])[C:35]([CH3:38])([CH3:37])[CH3:36])=[CH:24][CH:23]=1.C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[Cl:21][C:22]1[C:27]([C:28]([NH:19][C:14]2[CH:15]=[CH:16][CH:17]=[C:18]3[C:13]=2[N:12]=[CH:11][N:10]=[C:9]3[NH:8][CH:5]2[CH2:6][CH2:7][C:2]([F:1])([F:20])[CH2:3][CH2:4]2)=[O:29])=[C:26]([F:31])[C:25]([CH2:32][NH:33][C:34](=[O:39])[C:35]([CH3:37])([CH3:36])[CH3:38])=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 584833746-Chloro-2-fluoro-3-(pivalamidomethyl)benzoic acidHCID 86692230N4-(4,4-difluorocyclohexyl)quinazoline-4,8-diamine

Product 1

HCID 716788886-Chloro-N-(4-((4,4-difluorocyclohexyl)amino)quinazolin-8-yl)-2-fluoro-3-(pivalamidomethyl)benzamideYield 28.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared following the procedure described in Example-1 using N4-(4,4-difluorocyclohexyl)quinazoline-4,8-diamine (Intermediate-9, 75 mg, 0.27 mmol), 6-chloro-2-fluoro-3-(pivalamidomethyl)benzoic acid (Intermediate-2, 116 mg, 0.41 mmol), oxalyl chloride (78 mg, 0.62 mmol), DMF (1 drop) and DIPEA (105 mg, 0.81 mmol) in CH2Cl2 (5 mL) to afford 42 mg of the title product. 1H NMR (300 MHz, DMSO-d6): δ 10.40 (s, 1H), 8.69-8.66 (d, J=7.8 Hz, 1H), 8.49 (s, 1H), 8.12-8.09 (m, 2H), 7.53 (t, 1H), 7.40-7.32 (m, 2H), 4.28 (m, 3H), 2.09-1.98 (m, 6H), 1.73 (m, 2H), 1.12 (s, 9H); MS [M]+: 548.33.

Workup

  1. customThe title compound was prepared

Sources & evidence

ORD record
ord-f97ec4a89c59431ab41b0c4ff4cdd7ae
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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