Triethylamine → (4-Tert-butylsulfonylphenyl)-[1'-(trifluoromethyl)spiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl]methanone

HRID 1908144ノート

反応式

HRID 1908144 の反応式
[F:1][C:2]([F:22])([F:21])[C:3]1[N:11]2[C:6]([C:7]3([CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[O:8][C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=32)=[CH:5][CH:4]=1.[C:23]([S:27]([C:30]1[CH:38]=[CH:37][C:33]([C:34](O)=[O:35])=[CH:32][CH:31]=1)(=[O:29])=[O:28])([CH3:26])([CH3:25])[CH3:24].Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>ClCCl>[C:23]([S:27]([C:30]1[CH:31]=[CH:32][C:33]([C:34]([N:18]2[CH2:17][CH2:16][C:7]3([C:6]4=[CH:5][CH:4]=[C:3]([C:2]([F:1])([F:21])[F:22])[N:11]4[C:10]4[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=4[O:8]3)[CH2:20][CH2:19]2)=[O:35])=[CH:37][CH:38]=1)(=[O:29])=[O:28])([CH3:26])([CH3:25])[CH3:24]

参加物

6

反応物 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 596775524-(tert-Butylsulfonyl)benzoic acidHCID 674640241'-(Trifluoromethyl)spiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]

生成物 1

HCID 58551655(4-Tert-butylsulfonylphenyl)-[1'-(trifluoromethyl)spiro[piperidine-4,4'-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl]methanone収率 16.5%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

1′-(Trifluoromethyl)spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine] (172 mg, 0.559 mmol), 4-tert-butylsulfonylbenzoic acid (176 mg, 0.727 mmol), 3-(ethyliminomethyleneamino)-N,N-dimethyl-propan-1-amine hydrochloride (150 mg, 0.783 mmol), and triethylamine (312 μL, 2.24 mmol) were combined in dichloromethane (3.4 mL). The reaction mixture was allowed to stir for 72 hours at room temperature. The reaction mixture was washed three times with a 1M solution of hydrochloric acid, followed by three washes with a saturated aqueous solution of sodium bicarbonate, followed by three washes of a saturated aqueous solution of sodium chloride. The organic layer was dried over sodium sulfate, filtered, and evaporated to dryness to yield the crude product. The crude material was purified by reverse phase preparative chromatography utilizing a gradient of 10-99% acetonitrile in water to yield (4-tert-butylsulfonylphenyl)-[1′-(trifluoromethyl)spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl]methanone (49 mg, 16%) as a white solid. ESI-MS m/z calc. 532.2. found 533.5 (M+1)+. Retention time: 2.10 minutes (3 min run). 1H NMR (400 MHz, DMSO) δ 7.89 (d, J=8.0 Hz, 2H), 7.73 (d, J=8.0 Hz, 2H), 7.57 (d, J=8.0 Hz, 1H), 7.35-7.25 (m, 2H), 7.25-7.16 (m, 1H), 7.03 (d, J=3.9 Hz, 1H), 6.40 (d, J=3.9 Hz, 1H), 4.53-4.37 (m, 1H), 3.57-3.14 (m, 3H), 2.17-1.78 (m, 4H), 1.26 (s, 9H).

後処理

  1. washThe reaction mixture was washed three times with a 1M solution of hydrochloric acid
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customto yield the crude product
  6. customThe crude material was purified by reverse phase preparative chromatography

出典と根拠

ORDレコード
ord-7fbfa33992fe41babff86a78672c34ee
出典データセット
uspto-grants-2013_12
特許番号
US08598164B2

反応ノート

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