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

HRID 1469859Notes

Reaction equation

HRID 1469859 reaction equation
[F:1][C:2]([F:17])([F:16])[CH2:3][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.[Cl:18][C:19]1[C:24]([C:25](O)=[O:26])=[C:23]([F:28])[C:22]([CH2:29][NH:30][C:31](=[O:35])[CH:32]([CH3:34])[CH3:33])=[CH:21][CH:20]=1.S(Cl)(Cl)=O.CCN(C(C)C)C(C)C>C1COCC1>[Cl:18][C:19]1[C:24]([C:25]([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][CH2:3][C:2]([F:1])([F:16])[F:17])=[O:26])=[C:23]([F:28])[C:22]([CH2:29][NH:30][C:31](=[O:35])[CH:32]([CH3:33])[CH3:34])=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 866922656-Chloro-2-fluoro-3-(isobutyramidomethyl)benzoic acidHCID 86692308N4-(2,2,2-trifluoroethyl)quinazoline-4,8-diamine

Product 1

HCID 716800586-Chloro-2-fluoro-3-(isobutyramidomethyl)-N-(4-((2,2,2-trifluoroethyl)amino)quinazolin-8-yl)benzamideYield 12.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The title compound was prepared following the procedure described in Example-1 using N4-(2,2,2-trifluoroethyl)quinazoline-4,8-diamine (Intermediate-65, 70 mg, 0.29 mmol), 6-chloro-2-fluoro-3-(isobutyramidomethyl)benzoic acid (Intermediate-60, 118 mg, 0.43 mmol), thionyl chloride (1 mL), and DIPEA (148 mg, 1.15 mmol) in THF (2 mL) to afford 18 mg of the title product. 1H NMR (300 MHz, DMSO-d6): δ 10.57 (s, 1H), 8.93 (t, 1H), 8.76-8.73 (d, J=7.2 Hz, 1H), 8.61 (s, 1H), 8.38 (t, 1H), 8.12-8.09 (d, J=9.3 Hz, 1H), 7.66-7.61 (t, J=7.8 Hz, 1H), 7.40-7.38 (m, 2H), 4.47 (m, 2H), 4.32 (d, J=4.8 Hz, 2H), 2.42 (m, 1H), 1.05-1.03 (d, J=6.9 Hz, 6H); MS [M+H]+: 498.31.

Workup

  1. customThe title compound was prepared

Sources & evidence

ORD record
ord-5bd0ed03764746349e3ca23a6a6685f4
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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