Isobutyryl chloride → N-[4-(1-ethyl-4-{2-[4-(1-pyrrolidinylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)phenyl]-2-methylpropanamide

HRID 1180860ノート

反応式

HRID 1180860 の反応式
[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][C:15]([C:17]4[CH:22]=[CH:21][C:20]([CH2:23][N:24]5[CH2:28][CH2:27][CH2:26][CH2:25]5)=[CH:19][CH:18]=4)=[CH:16][C:9]=23)[C:5]([C:29]2[CH:35]=[CH:34][C:32]([NH2:33])=[CH:31][CH:30]=2)=[N:4]1)[CH3:2].[CH3:36][CH:37]([CH3:41])[C:38](Cl)=[O:39]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH2:1]([N:3]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[NH:14][C:15]([C:17]4[CH:18]=[CH:19][C:20]([CH2:23][N:24]5[CH2:28][CH2:27][CH2:26][CH2:25]5)=[CH:21][CH:22]=4)=[CH:16][C:9]=23)[C:5]([C:29]2[CH:30]=[CH:31][C:32]([NH:33][C:38](=[O:39])[CH:37]([CH3:41])[CH3:36])=[CH:34][CH:35]=2)=[N:4]1)[CH3:2]

参加物

5

反応物 2

HCID 62325Isobutyryl chlorideHCID 68995250HCID 68995250、化合物

生成物 1

HCID 58980014N-[4-(1-ethyl-4-{2-[4-(1-pyrrolidinylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)phenyl]-2-methylpropanamide収率 43%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒

実験手順

To a cloudy orange mixture of 4-(1-ethyl-4-{2-[4-(1-pyrrolidinylmethyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}-1H-pyrazol-3-yl)aniline (280 mg, 0.61 mmol) in dry CH2Cl2 (6 mL) was added TEA (253 uL, 1.82 mmol), DMAP (4 mg, 0.03 mmol) and 2-methylpropanoyl chloride (77 uL, 0.73 mmol). The reaction was stirred for 15 min at room temperature, quenched with water and diluted with CH2Cl2 and brine. The aqueous layer was extracted with CH2Cl2 followed by 1% MeOH in CH2Cl2 and the combined extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by Gilson reverse phase HPLC (MeCN/H2O with 0.1% TFA). The clean fractions were neutralized with aqueous NaHCO3, extracted with three portions of CH2Cl2 followed by 1% MeOH in CH2Cl2, dried (Na2SO4), filtered and concentrated under reduced pressure to give 139 mg (43%) of the title product as a yellow solid. ESMS [M+H]+: 533.4.

後処理

  1. customquenched with water
  2. additiondiluted with CH2Cl2 and brine
  3. extractionThe aqueous layer was extracted with CH2Cl2
  4. dry with materialthe combined extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by Gilson reverse phase HPLC (MeCN/H2O with 0.1% TFA)
  8. extractionextracted with three portions of CH2Cl2
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-ac663a242a0d4ee8a21624dee902bab8
出典データセット
uspto-grants-2007_10
特許番号
US07282588B2

反応ノート

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