Ethanol → HCID 71626969、化合物

HRID 1396399ノート

反応式

HRID 1396399 の反応式
[C:1]([C:5]1[N:10]=[C:9]([NH:11][C:12]2[CH:13]=[C:14]([NH:21][C@@H:22]3[CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]3[NH:28]C(=O)OC(C)(C)C)[N:15]=[N:16][C:17]=2[C:18](=[O:20])[NH2:19])[CH:8]=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O.C(O)C>ClCCl>[NH2:28][C@H:23]1[CH2:24][CH2:25][CH2:26][CH2:27][C@H:22]1[NH:21][C:14]1[N:15]=[N:16][C:17]([C:18]([NH2:19])=[O:20])=[C:12]([NH:11][C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[N:10]=2)[CH:13]=1

参加物

5

反応物 3

HCID 702EthanolHCID 6422Trifluoroacetic acidHCID 86689753HCID 86689753、化合物

生成物 1

HCID 71626969HCID 71626969、化合物収率 37.5%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of tert-butyl (1S,2R)-2-(5-(6-tert-butylpyridin-2-ylamino)-6-carbamoylpyridazin-3-ylamino)cyclohexylcarbamate (192 mg, 397 μmol) in dichloromethane (2 mL) was added TFA (747 mg, 505 μL, 6.55 mmol). After 14 h, the mixture was concentrated in vacuo then purified by chromatography (spherical silica, 50 g, 0-20% of a 9:1 MeOH:NH4OH solution in dichloromethane, 30 min) to give a pale brown gum. This was triturated with ethanol and concentrated to give a yellow solid. Trituration again with hot ethanol, followed by decanting of the supernatant, gave 6-((1R,2S)-2-aminocyclohexylamino)-4-(6-tert-butylpyridin-2-ylamino)pyridazine-3-carboxamide (57 mg, 149 μmol, 37%) as a cream powder after drying under high vacuum. 1H NMR (DMSO-d6) δ: 11.80 (s, 1H), 8.39 (d, J=2.0 Hz, 1H), 7.98 (s, 1H), 7.55-7.76 (m, 2H), 6.96-7.09 (m, 1H), 6.77 (dd, J=8.1, 0.5 Hz, 1H), 6.70 (d, J=8.1 Hz, 1H), 3.67 (br. s., 1H), 3.03-3.12 (m, 1H), 1.45-1.72 (m, 8H), 1.22-1.41 (m, 11H); MS (EI/CI) m/z: 384.2 [M+H].

後処理

  1. concentrationthe mixture was concentrated in vacuo
  2. customthen purified by chromatography (spherical silica, 50 g, 0-20% of a 9:1 MeOH:NH4OH solution in dichloromethane, 30 min)
  3. customto give a pale brown gum
  4. customThis was triturated with ethanol
  5. concentrationconcentrated
  6. customto give a yellow solid
  7. customby decanting of the supernatant

出典と根拠

ORDレコード
ord-13604f211919457bba84fe9e65c5cab3
出典データセット
uspto-grants-2014_12
特許番号
US08901124B2

反応ノート

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