tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate → HCID 86689773, 화합물

HRID 1396426노트

반응식

HRID 1396426 반응식
[C:1]([C:5]1[N:10]=[C:9]([NH:11][C:12]2[CH:17]=[C:16](Cl)[N:15]=[N:14][C:13]=2[C:19]([NH2:21])=[O:20])[CH:8]=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:22][C@@H:23]1[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]1[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33]>CN1C(=O)CCC1>[C:1]([C:5]1[N:10]=[C:9]([NH:11][C:12]2[CH:17]=[C:16]([NH:22][C@@H:23]3[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]3[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])[N:15]=[N:14][C:13]=2[C:19](=[O:20])[NH2:21])[CH:8]=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

참가 물질

4

반응물 2

HCID 68077633tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate3회HCID 86689752HCID 86689752, 화합물

생성물 1

HCID 86689773HCID 86689773, 화합물수율 46%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
130 °C

실험 절차

A resealable pressure tube was charged with 4-(6-tert-butylpyridin-2-ylamino)-6-chloropyridazine-3-carboxamide (100 mg, 327 μmol) dissolved in NMP (2.00 mL) To this solution was added tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (70.7 mg, 327 μmol) and the reaction mixture was heated in an oil bath with stirring at 130° C. for 24 h. Added additional tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (70.7 mg, 327 μmol) and reaction continued for 24 h. Added more tert-butyl (3R,4R)-4-aminotetrahydro-2H-pyran-3-ylcarbamate (70.7 mg, 327 μmol) and reaction continued for 72 h. The NMP was evaporated under high vacuum. The residue was purified by flash chromatography (silica gel 50 μm, 40 g, Analogix) eluting with 0 to 5% over 20 min (MeOH containing 10% NH4OH)/CH2Cl2 to yield tert-butyl (3R,4R)-4-(5-(6-tert-butylpyridin-2-ylamino)-6-carbamoylpyridazin-3-ylamino)tetrahydro-2H-pyran-3-ylcarbamate (73 mg, 46.0% yield) as a yellow foam. 1H NMR (CHLOROFORM-d) δ: 11.45 (br. s., 1H), 8.33 (s, 1H), 8.14 (s, 1H), 8.06 (d, J=3.4 Hz, 1H), 7.52 (t, J=7.9 Hz, 1H), 6.91 (d, J=7.9 Hz, 1H), 6.66 (d, J=7.9 Hz, 1H), 5.65 (br. s., 1H), 5.37 (d, J=8.3 Hz, 1H), 3.38-4.31 (m, 6H), 1.63-2.23 (m, 2H), 1.46 (s, 9H), 1.39 (s, 9H); LC-MS 486.3 [M+H]+.

후처리

  1. temperaturethe reaction mixture was heated in an oil bath
  2. additionAdded additional
  3. waitcontinued for 24 h
  4. additionAdded more
  5. waitcontinued for 72 h
  6. customThe NMP was evaporated under high vacuum
  7. customThe residue was purified by flash chromatography (silica gel 50 μm, 40 g, Analogix)
  8. washeluting with 0 to 5% over 20 min (MeOH containing 10% NH4OH)/CH2Cl2

출처 및 근거

ORD 기록
ord-df823e5e34fa408e87c32bcd93a6ccd6
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901124B2

반응 노트

불러오는 중…