(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → {(1S,2R)-2-[6-carbamoyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester

HRID 1396368노트

반응식

HRID 1396368 반응식
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]([NH2:10])=[O:9])=[C:4]([NH:11][C:12]2[N:17]=[C:16]3[N:18]([CH3:21])[CH:19]=[CH:20][C:15]3=[CH:14][CH:13]=2)[CH:3]=1.[NH2:22][C@@H:23]1[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]1[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33]>CN1CCCC1=O>[C:32]([O:31][C:30](=[O:36])[NH:29][C@H:24]1[CH2:25][CH2:26][CH2:27][CH2:28][C@H:23]1[NH:22][C:2]1[N:7]=[N:6][C:5]([C:8](=[O:9])[NH2:10])=[C:4]([NH:11][C:12]2[N:17]=[C:16]3[N:18]([CH3:21])[CH:19]=[CH:20][C:15]3=[CH:14][CH:13]=2)[CH:3]=1)([CH3:35])([CH3:33])[CH3:34]

참가 물질

4

반응물 2

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected2회HCID 86689730HCID 86689730, 화합물

생성물 1

HCID 86689731{(1S,2R)-2-[6-carbamoyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester수율 18%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

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온도
150 °C

실험 절차

6-Chloro-4-(1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-pyridazine-3-carboxylic acid amide (42 mg, 0.139 mmol), and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (89 mg, 0.416 mmol) were dissolved in N-methylpyrrolidinone (1.4 mL) and heated at 150° C. for 36 h. Additional tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (35 mg, 0.16 mmol) was added and the heating continued for 16 h more. The reaction mixture was cooled and concentrated in vacuo, then diluted with water, and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (sodium sulfate), filtered and concentrated in vacuo. Purification by chromatography (silica, 0 to 5% methanol in dichloromethane) gave {(1S,2R)-2-[6-carbamoyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (12 mg, 18%) as a light brown amorphous residue. LCMS (EI/CI) m/z: 481 [M+H].

후처리

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated in vacuo
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by chromatography (silica, 0 to 5% methanol in dichloromethane)

출처 및 근거

ORD 기록
ord-76448f7d08ca46adbe9ee60d46d18c40
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901124B2

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