Butanoic acid, 4-chloro-4-oxo-, ethyl ester → HCID 11569937, compound

HRID 1364501Notes

Reaction equation

[NH2:1][C:2]1[N:6]([C:7](=[O:16])[C:8]2[C:13]([F:14])=[CH:12][CH:11]=[CH:10][C:9]=2[F:15])[N:5]=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([S:24]([NH2:27])(=[O:26])=[O:25])=[CH:20][CH:19]=2)[N:3]=1.CC(C)([O-])C.[K+].Cl[C:35](=[O:43])[CH2:36][CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39]>C1COCC1>[CH2:41]([O:40][C:38](=[O:39])[CH2:37][CH2:36][C:35]([NH:27][S:24]([C:21]1[CH:22]=[CH:23][C:18]([NH:17][C:4]2[N:3]=[C:2]([NH2:1])[N:6]([C:7](=[O:16])[C:8]3[C:13]([F:14])=[CH:12][CH:11]=[CH:10][C:9]=3[F:15])[N:5]=2)=[CH:19][CH:20]=1)(=[O:25])=[O:26])=[O:43])[CH3:42]

Participants

Conditions

Temperature: 0 °C

Procedure

To a nitrogen purged flask was added 4-[5-amino-1-(2,6-difluorobenzoyl)-1H-[1,2,4]triazol-3-ylamino]-benzenesulfonamide Compound 1a (1.0 g, 2.5 mmol) and THF (100 mL). The mixture was cooled to 0° C. and potassium tert-butoxide (2.8 mL, 1.0 M solu in THF) was added dropwise. After addition the mixture was stirred at 0° C. for 1 hr, then ethyl 4-chloro-4-oxobutyrate (0.46 g in 10 mL THF, 2.8 mmol) was added dropwise. The stirring was continued for 30 min, then the mixture was warmed to rt and stirred overnight. After being concentrated, the residue was purified by flash chromatography (silica gel, CH2Cl2:MeOH/9:1) to afford the desired product (200 mg, 15%) as a white solid. 1H NMR (300 MHz, CD3OD) δ 7.72 (d, 2H), 7.70 (m, 1H), 7.50 (d, 2H), 7.15 (t, 2H), 4.20 (q, 2H), 3.32 (s, 2H), 2.71 (s, 2H), 1.25 (t, 2H); MS (ESI) m/z: 523 (M+H)+.

Workup

additionAfter addition the mixture
waitThe stirring was continued for 30 min
temperaturethe mixture was warmed to rt
stirringstirred overnight
concentrationAfter being concentrated
customthe residue was purified by flash chromatography (silica gel, CH2Cl2:MeOH/9:1)

Sources & evidence

ORD record: ord-7b870005943d45a3b1fef33179857462
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07888380B2

Reaction notes

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