Oxalyl chloride → N-(4-(tert-Butylamino)quinazolin-8-yl)-2-(difluoromethyl)-5-(isobutyramidomethyl)nicotinamide

HRID 1469861Notes

Reaction equation

HRID 1469861 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].[F:17][CH:18]([F:35])[C:19]1[N:27]=[CH:26][C:25]([CH2:28][NH:29][C:30](=[O:34])[CH:31]([CH3:33])[CH3:32])=[CH:24][C:20]=1[C:21](O)=[O:22].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:21](=[O:22])[C:20]3[CH:24]=[C:25]([CH2:28][NH:29][C:30](=[O:34])[CH:31]([CH3:33])[CH3:32])[CH:26]=[N:27][C:19]=3[CH:18]([F:35])[F:17])[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 710598402-(Difluoromethyl)-5-(isobutyramidomethyl)nicotinic acidHCID 86692301N4-(tert-butyl)quinazoline-4,8-diamine

Product 1

HCID 71680227N-(4-(tert-Butylamino)quinazolin-8-yl)-2-(difluoromethyl)-5-(isobutyramidomethyl)nicotinamideYield 5.5%

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), 2-(difluoromethyl)-5-(isobutyramidomethyl)nicotinic acid (Intermediate-66, 150 mg, 0.55 mmol), oxalyl chloride (104 mg, 0.83 mmol), DMF (1 drop) and DIPEA (178 mg, 1.38 mmol) in CH2Cl2 (2 mL) to afford 12 mg of the title product. 1H NMR (300 MHz, DMSO-d6): δ 10.32 (s, 1H), 8.71 (s, 1H), 8.63 (m, 1H), 8.49 (m, 2H), 8.16 (d, 1H), 8.05 (m, 1H), 7.46 (m, 2H), 7.22 (t, J=54 Hz, 1H), 4.42 (d, 2H), 1.55 (s, 9H), 1.05 (d, J=6.6 Hz, 6H); MS [M+H]+: 471.49.

Workup

  1. customThe title compound was prepared

Sources & evidence

ORD record
ord-67a9824fdbb94d6d9a27913abd2d1066
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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