Diisobutylaluminumhydride → N-(7-(5-fluoro-4-(hydroxymethyl)-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 1502483ノート

反応式

HRID 1502483 の反応式
[H-].C([Al+]CC(C)C)C(C)C.[CH:11]1([C:14]([NH:16][C:17]2[N:18]=[CH:19][C:20]3[C:25]([CH:26]=2)=[CH:24][CH:23]=[C:22]([C:27]2[C:36]([CH3:37])=[CH:35][C:30]([C:31](OC)=[O:32])=[C:29]([F:38])[CH:28]=2)[CH:21]=3)=[O:15])[CH2:13][CH2:12]1>C1COCC1>[F:38][C:29]1[C:30]([CH2:31][OH:32])=[CH:35][C:36]([CH3:37])=[C:27]([C:22]2[CH:21]=[C:20]3[C:25]([CH:26]=[C:17]([NH:16][C:14]([CH:11]4[CH2:13][CH2:12]4)=[O:15])[N:18]=[CH:19]3)=[CH:24][CH:23]=2)[CH:28]=1

参加物

4

反応物 2

HCID 21225700DiisobutylaluminumhydrideHCID 67974657Methyl 4-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-2-fluoro-5-methylbenzoate

生成物 1

HCID 67974756N-(7-(5-fluoro-4-(hydroxymethyl)-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide収率 57.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-15 °C

実験手順

Diisobutylaluminum hydride (1.0 mol/L) in THF (1.1 mL, 1.06 mmol) was added dropwise to a solution of methyl 4-[3-(cyclopropanecarbonylamino)-7-isoquinolyl]-2-fluoro-5-methyl-benzoate (100 mg, 0.26 mmol) in THF (1 mL) cooled at −15° C. The reaction mixture warmed to room temperature. After 1 hour, the reaction mixture was quenched with saturated aqueous ammonium chloride, diluted with ethyl acetate (50 mL) and washed with 1.0M citric acid solution in water (20 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue that was purified by reverse phase HPLC (5-85% acetonitrile in water w/0.1% NH4OH, 14 minutes). Desired fractions were combined and evaporated in vacuo to afford the title compound as a white solid (52 mg, 56%). 1H NMR (400 MHz, DMSO) δ 10.90 (s, 1H), 9.17 (s, 1H), 8.49 (s, 1H), 8.02 (s, 1H), 7.92 (d, J=8.6 Hz, 1H), 7.69 (dd, J=8.5, 1.6 Hz, 1H), 7.42 (d, J=7.7 Hz, 1H), 7.11 (d, J=10.7 Hz, 1H), 5.26 (s, 1H), 4.58 (s, 2H), 2.26 (s, 3H), 2.13-2.03 (m, 1H), 0.92-0.77 (m, 4H). LCMS (Method E): RT=4.595 min, M+H+=351.2.

後処理

  1. temperatureThe reaction mixture warmed to room temperature
  2. customthe reaction mixture was quenched with saturated aqueous ammonium chloride
  3. additiondiluted with ethyl acetate (50 mL)
  4. washwashed with 1.0M citric acid solution in water (20 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto provide a residue that
  10. customwas purified by reverse phase HPLC (5-85% acetonitrile in water w/0.1% NH4OH, 14 minutes)
  11. customevaporated in vacuo

出典と根拠

ORDレコード
ord-90c21359ee254887a6812a1480d5da3d
出典データセット
uspto-grants-2015_12
特許番号
US09206175B2

反応ノート

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