Trifluoroacetic acid → HCID 71626161、化合物

HRID 1396395ノート

反応式

HRID 1396395 の反応式
[C:1]([C:4]1[N:9]=[N:8][C:7]([NH:10][C@@H:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@@H:12]2[NH:17]C(=O)OC(C)(C)C)=[CH:6][C:5]=1[NH:25][C:26]1[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]([CH3:33])[N:27]=1)(=[O:3])[NH2:2].[F:34][C:35]([F:40])([F:39])[C:36]([OH:38])=[O:37]>ClCCl>[F:34][C:35]([F:40])([F:39])[C:36]([OH:38])=[O:37].[NH2:17][C@H:12]1[CH2:13][CH2:14][CH2:15][CH2:16][C@H:11]1[NH:10][C:7]1[N:8]=[N:9][C:4]([C:1]([NH2:2])=[O:3])=[C:5]([NH:25][C:26]2[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]([CH3:33])[N:27]=2)[CH:6]=1

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 86689750tert-butyl (1S,2R)-2-(6-carbamoyl-5-(4,6-dimethylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate

生成物 1

HCID 71626161HCID 71626161、化合物収率 43%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of tert-butyl (1S,2R)-2-(6-carbamoyl-5-(4,6-dimethylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (75 mg, 165 μmol) in dichloromethane (5 mL) was added trifluoroacetic acid (1.88 g, 1.27 mL, 16.5 mmol) and the mixture stirred at room temperature for 16 h. The mixture was concentrated and then the residue was diluted with dichloromethane and neutralized with NH4OH. Purification by chromatography (silica, 0-100% of a 10:0.5:89.5 methanol:NH4OH:dichloromethane in dichloromethane) followed by further purification by HPLC (C-18, 10-100% water in acetonitrile gradient) gave 6-((1R,2S)-2-aminocyclohexylamino)-4-(4,6-dimethylpyridin-2-ylamino)pyridazine-3-carboxamide 2,2,2-trifluoroacetate (33 mg, 70.3 μmol, 43%) as a fluffy off white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.66 (s, 1H), 8.38 (s, 1H), 8.25 (s, 1H), 7.86 (br. s, 1H), 7.40 (br. s, 2H), 6.76 (s, 1H), 6.65 (s, 1H), 4.40 (s., 1H), 3.63 (s, 1H), 2.48 (s, 3H), 1.58-1.86 (m, 8H), 1.46 (m, 2H); MS (EI/CI) m/z: 356.1 [M+H].

後処理

  1. concentrationThe mixture was concentrated
  2. additionthe residue was diluted with dichloromethane and neutralized with NH4OH
  3. customPurification by chromatography (silica, 0-100% of a 10:0.5:89.5 methanol:NH4OH:dichloromethane in dichloromethane)
  4. customfollowed by further purification by HPLC (C-18, 10-100% water in acetonitrile gradient)

出典と根拠

ORDレコード
ord-58eadd1a0b064a48bcccdf246ffd870e
出典データセット
uspto-grants-2014_12
特許番号
US08901124B2

反応ノート

読み込み中…