Ethanol → HCID 71626969, 화합물

HRID 1396399노트

반응식

HRID 1396399 반응식
[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

참가 물질

5

반응물 3

HCID 702EthanolHCID 6422Trifluoroacetic acidHCID 86689753HCID 86689753, 화합물

생성물 1

HCID 71626969HCID 71626969, 화합물수율 37.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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].

후처리

  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

출처 및 근거

ORD 기록
ord-13604f211919457bba84fe9e65c5cab3
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901124B2

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