Trifluoroacetic acid → HCID 71626103、化合物

HRID 1396490ノート

反応式

HRID 1396490 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][O: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]=[CH:30][C:29]([CH:32]([CH3:34])[CH3:33])=[C:28]([O:35][CH3:36])[N:27]=1)(=[O:3])[NH2:2].FC(F)(F)C(O)=O>ClCCl.[NH4+].[OH-].O>[NH2:17][C@@H:12]1[C@H:11]([NH:10][C:7]2[N:8]=[N:9][C:4]([C:1]([NH2:2])=[O:3])=[C:5]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([CH:32]([CH3:34])[CH3:33])=[C:28]([O:35][CH3:36])[N:27]=3)[CH:6]=2)[CH2:16][CH2:15][O:14][CH2:13]1

参加物

6

反応物 2

HCID 6422Trifluoroacetic acidHCID 86689814HCID 86689814、化合物

生成物 1

HCID 71626103HCID 71626103、化合物収率 31%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回HCID 14923Ammonium Hydroxide溶媒

実験手順

To a solution of tert-butyl (3R,4R)-4-(6-carbamoyl-5-(5-isopropyl-6-methoxypyridin-2-ylamino)pyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (141 mg, 281 μmol) in dichloromethane (4.3 mL) was added trifluoroacetic acid (641 mg, 433 μL, 5.62 mmol) and the mixture stirred at room temperature for 16 h. The mixture was diluted with 25% aqueous NH4OH, dichloromethane, and water. The organic phase was separated and washed with water (2×), then concentrated in vacuo and purified by chromatography (silica, 3 to 10% of a 99.5:0.5 methanol:NH4OH solution in dichloromethane) to give 6-((3R,4R)-3-aminotetrahydro-2H-pyran-4-ylamino)-4-(5-isopropyl-6-methoxypyridin-2-ylamino)pyridazine-3-carboxamide (35 mg, 87 μmol, 31%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.53 (s, 1H), 8.37 (s, 1H), 7.70 (s, 1H), 7.62 (s, 1H), 7.54 (d, J=8.1 Hz, 1H), 6.80 (d, J=7.8 Hz, 1H), 6.54 (d, J=8.0 Hz, 1H), 4.05 (br. s, 1H), 3.81 (d, J=11.9 Hz, 1H), 3.67 (dd, J=10.9, 3.5 Hz, 1H), 3.49 (dd, J=11.1. 1.9 Hz, 1H), 3.37 (m, 2H), 3.08 (m, 1H), 2.97 (s, 1H), 1.81 (m, 1H), 1.65 (m, 1H), 1.16 (d, J=6.8 Hz, 6H); MS (EI/CI) m/z: 402.3 [M+H].

後処理

  1. customThe organic phase was separated
  2. washwashed with water (2×)
  3. concentrationconcentrated in vacuo
  4. custompurified by chromatography (silica, 3 to 10% of a 99.5:0.5 methanol:NH4OH solution in dichloromethane)

出典と根拠

ORDレコード
ord-ef16cba9147740dda9ca454f0513a46b
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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