Trifluoroacetic acid → HCID 71626103, 화합물

HRID 1396490노트

반응식

HRID 1396490 반응식
[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

참가 물질

6

반응물 2

HCID 6422Trifluoroacetic acidHCID 86689814HCID 86689814, 화합물

생성물 1

HCID 71626103HCID 71626103, 화합물수율 31%

시약·촉매·용매 3

HCID 962Water용매HCID 6344Dichloromethane용매2회HCID 14923Ammonium Hydroxide용매

실험 절차

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].

후처리

  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)

출처 및 근거

ORD 기록
ord-ef16cba9147740dda9ca454f0513a46b
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901124B2

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