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

HRID 1396426ノート

反応式

HRID 1396426 の反応式
[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]

参加物

4

反応物 2

HCID 68077633tert-Butyl ((3R,4R)-4-aminotetrahydro-2H-pyran-3-yl)carbamate3 回HCID 86689752HCID 86689752、化合物

生成物 1

HCID 86689773HCID 86689773、化合物収率 46%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
130 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-df823e5e34fa408e87c32bcd93a6ccd6
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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