Triethylamine → ethyl 4-(3-(2-(methylsulfonamidomethyl)acrylamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

HRID 882142ノート

反応式

HRID 882142 の反応式
[NH2:1][CH2:2][C:3](=[CH2:27])[C:4]([NH:6][C:7]1[CH:8]=[C:9]([C:13]2[C:14]3[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:20][NH:19][C:15]=3[N:16]=[CH:17][N:18]=2)[CH:10]=[CH:11][CH:12]=1)=[O:5].C(N(CC)CC)C.[CH3:35][S:36](Cl)(=[O:38])=[O:37]>C(Cl)Cl>[CH3:35][S:36]([NH:1][CH2:2][C:3](=[CH2:27])[C:4]([NH:6][C:7]1[CH:8]=[C:9]([C:13]2[C:14]3[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:20][NH:19][C:15]=3[N:16]=[CH:17][N:18]=2)[CH:10]=[CH:11][CH:12]=1)=[O:5])(=[O:38])=[O:37]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 89630004ethyl 4-(3-(2-(aminomethyl)acrylamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

生成物 1

HCID 89630035ethyl 4-(3-(2-(methylsulfonamidomethyl)acrylamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of ethyl 4-(3-(2-(aminomethyl)acrylamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (32 mg, 0.088 mmol) in DCM (438 μL) was added triethylamine (12 μL, 0.088 mmol) and methanesulfonyl chloride (7.5 μL, 0.096 mmol) at 0° C. The reaction mixture was allowed to stir at 0° C. for 1 hour and then gradually warmed up to room temperature over 1 hour. The resulting mixture was diluted with DCM (2 mL) and washed with saturated aqueous sodium bicarbonate solution (2 mL). The aqueous layer was extracted with DCM (×3) and the combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by reverse phase HPLC using an acetonitrile gradient in water with 0.1% TFA modifier to give ethyl 4-(3-(2-(methylsulfonamidomethyl)acrylamido)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate. LRMS (ESI) calc'd for C20H22N5O5S [M+H]+: 444, found 444. 1H NMR (600 MHz, DMSO-D6) δ 12.99 (bs, 1H), 10.11 (s, 1H), 8.90 (s, 1H), 8.30 (s, 1H), 8.05 (s, 1H), 7.84 (d, J=8.21 Hz, 1H), 7.42 (t, J=8.21 Hz, 1H), 7.38 (t, J=6.45 Hz, 1H), 7.33 (d, J=7.63 Hz, 1H), 6.01 (s, 1H), 5.75 (s, 1H), 3.89 (d, J=6.45 Hz, 2H), 3.86 (q, J=7.04 Hz, 2H), 2.94 (s, 3H), 0.86 (t, J=7.04 Hz, 3H).

後処理

  1. temperaturegradually warmed up to room temperature over 1 hour
  2. washwashed with saturated aqueous sodium bicarbonate solution (2 mL)
  3. extractionThe aqueous layer was extracted with DCM (×3)
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by reverse phase HPLC

出典と根拠

ORDレコード
ord-3f54b1b062c64778a8e7a3966c7206dd
出典データセット
uspto-grants-2015_03
特許番号
US08993756B2

反応ノート

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