Thionyl Chloride → 6-Chloro-2-fluoro-3-(isobutyramidomethyl)-N-(4-(isopropylamino)quinazolin-8-yl)benzamide

HRID 1469863Notes

Reaction equation

HRID 1469863 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].[Cl:16][C:17]1[C:22]([C:23](O)=[O:24])=[C:21]([F:26])[C:20]([CH2:27][NH:28][C:29](=[O:33])[CH:30]([CH3:32])[CH3:31])=[CH:19][CH:18]=1.S(Cl)(Cl)=O.CCN(C(C)C)C(C)C>C1COCC1>[Cl:16][C:17]1[C:22]([C:23]([NH:15][C:10]2[CH:11]=[CH:12][CH:13]=[C:14]3[C:9]=2[N:8]=[CH:7][N:6]=[C:5]3[NH:4][CH:1]([CH3:3])[CH3:2])=[O:24])=[C:21]([F:26])[C:20]([CH2:27][NH:28][C:29](=[O:33])[CH:30]([CH3:31])[CH3:32])=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 866922656-Chloro-2-fluoro-3-(isobutyramidomethyl)benzoic acidHCID 86692303N4-isopropylquinazoline-4,8-diamine

Product 1

HCID 716802296-Chloro-2-fluoro-3-(isobutyramidomethyl)-N-(4-(isopropylamino)quinazolin-8-yl)benzamideYield 17.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The title compound was prepared following the procedure described in Example-1 using N4-isopropylquinazoline-4,8-diamine (Intermediate-57, 50 mg, 0.25 mmol), 6-chloro-2-fluoro-3-(isobutyramidomethyl)benzoic acid (Intermediate-60, 100 mg, 0.37 mmol), thionyl chloride (1 mL), and DIPEA (127 mg, 0.99 mmol) in THF (2 mL) to afford 20 mg of the title product. 1H NMR (300 MHz, DMSO-d6): δ 10.42 (s, 1H), 8.70-8.67 (d, J=7.2 Hz, 1H), 8.48 (s, 1H), 8.37 (t, 1H), 8.11-8.08 (d, J=7.8 Hz, 2H), 7.53 (t, 1H), 7.41 (m, 2H), 4.55 (m, 1H), 4.31 (d, 2H), 2.50 (m, 1H), 1.27 (d, J=6.6 Hz, 6H), 1.05-1.03 (d, J=6.9 Hz, 6H); MS [M+H]+: 458.47.

Workup

  1. customThe title compound was prepared

Sources & evidence

ORD record
ord-6b175323b57c4034b7b2f0872ce9c875
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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