Sodium hydride → ethyl 1-amino-4-{4-[(tert-butoxycarbonyl)amino]-3-fluorophenyl}-5-cyano-1H-pyrrole-3-carboxylate

HRID 73657ノート

反応式

HRID 73657 の反応式
[H-].[Na+].[C:3]([O:7][C:8]([NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:18]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:19][NH:20][C:21]=2[C:22]#[N:23])=[CH:13][C:12]=1[F:29])=[O:9])([CH3:6])([CH3:5])[CH3:4].[NH2:30]OP(=O)(C1C=CC=CC=1)C1C=CC=CC=1>CN(C=O)C>[NH2:30][N:20]1[C:21]([C:22]#[N:23])=[C:17]([C:14]2[CH:15]=[CH:16][C:11]([NH:10][C:8]([O:7][C:3]([CH3:6])([CH3:5])[CH3:4])=[O:9])=[C:12]([F:29])[CH:13]=2)[C:18]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:19]1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 10955453O-(Diphenylphosphinyl)hydroxylamineHCID 57955228Ethyl 4-{4-[(tert-butoxycarbonyl)amino]-3-fluorophenyl}-5-cyano-1H-pyrrole-3-carboxylate

生成物 1

HCID 57955353ethyl 1-amino-4-{4-[(tert-butoxycarbonyl)amino]-3-fluorophenyl}-5-cyano-1H-pyrrole-3-carboxylate

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A 1-L 3-neck rbf was fitted with an overhead stirrer and charged with sodium hydride (60% dispersion in mineral oil, 2.19 g, 54.6 mmol) and DMF (550 mL). Ethyl 4-{4-[(tert-butoxycarbonyl)amino]-3-fluorophenyl}-5-cyano-1H-pyrrole-3-carboxylate (10.00 g, 45.5 mmol) was added and the mixture was left to stir at rt for 15 min. The reaction mixture was treated with (aminooxy)(diphenyl) phosphine oxide (12.74 g, 54.6 mmol) and heated to 60° C. The very thick reaction mixture gradually became a readily stirred suspension. After 1 h analysis by RP-HPLC indicated that all starting material had been consumed. The reaction was cooled to rt and diluted with 1.5 L EtOAc and aq. sodium bicarbonate. The aqueous layer was back extracted with EtOAc (2×) and the combined organic layers were dried (sodium sulfate) and filtered through a silica plug. Trituration with ether:hexanes (1:2) gave the title compound as a yellowish powder (18.06 g, 46.5 mmol, 93.7%). 1H-NMR (DMSO-d6) δ 9.13 (s, 1H), 7.68 (s, 1H, 7.68 (t, J=8 Hz, 1H), 7.29 (dd, J=12, 2 Hz, 1H), 7.19 (dd, J=8 Hz, 1H), 6.67 (s, 2H), 4.14 (q, J=7 Hz, 2H), 1.50 (s, 9H), 1.18 (s, 3H); MS [M+Na]+=411.0; LCMS RT=3.48.

後処理

  1. customA 1-L 3-neck rbf was fitted with an overhead stirrer
  2. waitthe mixture was left
  3. temperatureheated to 60° C
  4. waitAfter 1 h analysis by RP-HPLC indicated that all starting material
  5. customhad been consumed
  6. temperatureThe reaction was cooled to rt
  7. additiondiluted with 1.5 L EtOAc and aq. sodium bicarbonate
  8. extractionThe aqueous layer was back extracted with EtOAc (2×)
  9. dry with materialthe combined organic layers were dried (sodium sulfate)
  10. filtrationfiltered through a silica plug

出典と根拠

ORDレコード
ord-8be5735a7d4442afb66d5054a56516ba
出典データセット
uspto-grants-2014_09
特許番号
US08829185B2

反応ノート

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