Ethanol → 4-Fluoro-6-{2-(methylamino)-6-[(3R)-3-methyl-4-morpholinyl]-4-pyrimidinyl}-1H-indazol-3-amine

HRID 2367535ノート

反応式

HRID 2367535 の反応式
F[C:2]1[CH:9]=[C:8]([C:10]2[CH:15]=[C:14]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][C@H:17]3[CH3:22])[N:13]=[C:12]([NH:23][CH3:24])[N:11]=2)[CH:7]=[C:6]([F:25])[C:3]=1[C:4]#[N:5].[NH2:26][NH2:27].CCN(C(C)C)C(C)C.C(O)C>O.CCOC(C)=O>[F:25][C:6]1[CH:7]=[C:8]([C:10]2[CH:15]=[C:14]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][C@H:17]3[CH3:22])[N:13]=[C:12]([NH:23][CH3:24])[N:11]=2)[CH:9]=[C:2]2[C:3]=1[C:4]([NH2:5])=[N:26][NH:27]2

参加物

7

反応物 4

HCID 702EthanolHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 585047102,6-Difluoro-4-{2-(methylamino)-6-[(3R)-3-methyl-4-morpholinyl]-4-pyrimidinyl}benzonitrile

生成物 1

HCID 462151264-Fluoro-6-{2-(methylamino)-6-[(3R)-3-methyl-4-morpholinyl]-4-pyrimidinyl}-1H-indazol-3-amine収率 68.6%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
150 °C

実験手順

A 2-mL microwave vial was charged with 2,6-difluoro-4-{2-(methylamino)-6-[(3R)-3-methyl-4-morpholinyl]-4-pyrimidinyl}benzonitrile (75 mg, 0.217 mmol), hydrazine (0.027 mL, 0.869 mmol), Hunig's base (0.152 mL, 0.869 mmol) and ethanol (1 mL). The reaction mixture was heated at 150° C. for 15 minutes in a microwave reactor. The reaction mixture was allowed to cool, then was poured into EtOAc (50 mL) and water (25 mL). The aqueous layer was extracted with two further portion of EtOAc (2×50 mL), and the combined organics dried over Na2SO4. The dried solution was filtered and concentrated, and the resulting residue was purified by RP-HPLC (0-30% CH3CN in H2O, 0.1% TFA) to afford the title compound (53.2 mg) as a yellow solid. LC-MS (ES) m/z=358 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.19 (d, J=6.6 Hz, 3H), 2.83 (bs, 3H), 3.06-3.20 (m, 1H), 3.40-3.52 (m, 1H), 3.55-3.66 (m, 1H), 3.69-3.78 (m, 1H), 3.88-4.00 (m, 1H), 4.06-4.24 (m, 1H), 4.43-4.62 (m, 1H), 5.27 (bs, 2H), 6.45-6.71 (m, 2H), 7.26-7.49 (m, 1H), 7.76-7.96 (m, 1H), 11.71-12.13 (m, 1H).

後処理

  1. temperatureto cool
  2. extractionThe aqueous layer was extracted with two further portion of EtOAc (2×50 mL)
  3. dry with materialthe combined organics dried over Na2SO4
  4. filtrationThe dried solution was filtered
  5. concentrationconcentrated
  6. customthe resulting residue was purified by RP-HPLC (0-30% CH3CN in H2O, 0.1% TFA)

出典と根拠

ORDレコード
ord-8eb2e9a9bcbe4737acd9d0e648471ade
出典データセット
uspto-grants-2014_04
特許番号
US08697685B2

反応ノート

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