Oxalyl chloride → 2-(Difluoromethyl)-5-(isobutyramidomethyl)-N-(4-(isopropylamino)quinazolin-8-yl)nicotinamide

HRID 1469862Notes

Reaction equation

HRID 1469862 reaction equation
[CH:1]([NH:4][C:5]1[C:14]2[C:9](=[C:10]([NH2:15])[CH:11]=[CH:12][CH:13]=2)[N:8]=[CH:7][N:6]=1)([CH3:3])[CH3:2].[F:16][CH:17]([F:34])[C:18]1[N:26]=[CH:25][C:24]([CH2:27][NH:28][C:29](=[O:33])[CH:30]([CH3:32])[CH3:31])=[CH:23][C:19]=1[C:20](O)=[O:21].C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[F:34][CH:17]([F:16])[C:18]1[N:26]=[CH:25][C:24]([CH2:27][NH:28][C:29](=[O:33])[CH:30]([CH3:31])[CH3:32])=[CH:23][C:19]=1[C:20]([NH:15][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:9]=1[N:8]=[CH:7][N:6]=[C:5]2[NH:4][CH:1]([CH3:3])[CH3:2])=[O:21]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 710598402-(Difluoromethyl)-5-(isobutyramidomethyl)nicotinic acidHCID 86692303N4-isopropylquinazoline-4,8-diamine

Product 1

HCID 716802282-(Difluoromethyl)-5-(isobutyramidomethyl)-N-(4-(isopropylamino)quinazolin-8-yl)nicotinamideYield 4.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared following the procedure described in Example-1 using N4-isopropylquinazoline-4,8-diamine (Intermediate-57, 100 mg, 0.50 mmol), 2-(difluoromethyl)-5-(isobutyramidomethyl)nicotinic acid (Intermediate-66, 161 mg, 0.60 mmol), oxalyl chloride (113 mg, 0.90 mmol), DMF (1 drop) and DIPEA (192 mg, 1.49 mmol) in CH2Cl2 (2 mL) to afford 10 mg of the title product. 1H NMR (300 MHz, DMSO-d6): δ 10.32 (s, 1H), 8.71 (s, 1H), 8.64 (m, 1H), 8.48 (m, 2H), 8.08 (m, 3H), 7.53 (m, 1H), 7.23 (t, J=54 Hz, 1H), 4.44 (m, 1H), 4.41 (d, 2H), 2.50 (m, 1H), 1.27 (d, J=6.9 Hz, 6H), 1.04 (d, J=7.5 Hz, 6H); MS [M+H]+: 457.47.

Workup

  1. customThe title compound was prepared

Sources & evidence

ORD record
ord-e024138fe08046e49637717465b01921
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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