3-Fluorobenzenesulfonyl Chloride → 4-{[4-(3-Fluorobenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl]-amino}-benzoic acid

HRID 1360258노트

반응식

HRID 1360258 반응식
C([O:3][C:4](=[O:24])[C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([C:14]2[CH:15]=[CH:16][C:17]3[O:22][CH2:21][CH2:20][NH:19][C:18]=3[CH:23]=2)=[O:13])=[CH:7][CH:6]=1)C.[F:25][C:26]1[CH:27]=[C:28]([S:32](Cl)(=[O:34])=[O:33])[CH:29]=[CH:30][CH:31]=1>N1C=CC=CC=1>[F:25][C:26]1[CH:27]=[C:28]([S:32]([N:19]2[C:18]3[CH:23]=[C:14]([C:12]([NH:11][C:8]4[CH:9]=[CH:10][C:5]([C:4]([OH:3])=[O:24])=[CH:6][CH:7]=4)=[O:13])[CH:15]=[CH:16][C:17]=3[O:22][CH2:21][CH2:20]2)(=[O:34])=[O:33])[CH:29]=[CH:30][CH:31]=1

참가 물질

4

반응물 2

HCID 27342583-Fluorobenzenesulfonyl ChlorideHCID 667888474-[(3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl)-amino]-benzoic acid ethyl ester

생성물 1

HCID 247625524-{[4-(3-Fluorobenzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl]-amino}-benzoic acid수율 44.1%

시약·촉매·용매 1

HCID 1049Pyridine용매2회

실험 절차

Step 7 and 8. A solution of 4-[(3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl)-amino]-benzoic acid ethyl ester (27 mg, 0.085 mmol) in pyridine (0.4 mL) was treated with a solution of 3-fluoro-benzenesulfonyl chloride (25 mg, 0.13 mmol) in pyridine (0.2 mL). The resulting mixture was stirred at room temperature for 18 hours. The pyridine was evaporated, and the residual crude 4-{[4-(3-fluoro-benzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl]-amino}-benzoic acid ethyl ester was dissolved in ethanol (0.6 mL) and treated with KOH 3N (0.15 mL). The resulting mixture was stirred at room temperature overnight. The mixture was acidified with HCl 3N and evaporated. The residue was purified by preparative HPLC (ZORBAX Eclipse XDB-C18, 21.2×50 mm, 5 μm, gradient acetonitrile/water+0.1% formic acid). 4-{[4-(3-Fluoro-benzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl]-amino}-benzoic acid (17.1 mg, 44%) was obtained as an off-white solid, MS (ISP): m/e=455.0 (M−H).

후처리

  1. customThe pyridine was evaporated
  2. dissolutionthe residual crude 4-{[4-(3-fluoro-benzenesulfonyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbonyl]-amino}-benzoic acid ethyl ester was dissolved in ethanol (0.6 mL)
  3. additiontreated with KOH 3N (0.15 mL)
  4. stirringThe resulting mixture was stirred at room temperature overnight
  5. customevaporated
  6. customThe residue was purified by preparative HPLC (ZORBAX Eclipse XDB-C18, 21.2×50 mm, 5 μm, gradient acetonitrile/water+0.1% formic acid)

출처 및 근거

ORD 기록
ord-7721f61db1de4fffab6d49d310d7e4e1
출처 데이터셋
uspto-grants-2011_02
특허 번호
US07879845B2

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