Potassium Phosphate, Tribasic → Tert-butyl 4-[4-[5-(1,3-benzoxazol-2-yl)-6-(bis(tert-butoxycarbonyl)amino)-3-pyridyl]-3-(methoxymethyl)pyrazol-1-yl]piperidine-1-carboxylate

HRID 908402ノート

反応式

HRID 908402 の反応式
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([N:25]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[N:12][CH:13]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:15]=1.Br[C:41]1[C:42]([CH2:59][O:60][CH3:61])=[N:43][N:44]([CH:46]2[CH2:51][CH2:50][N:49]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[CH2:48][CH2:47]2)[CH:45]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:15]=[C:14]([C:41]2[C:42]([CH2:59][O:60][CH3:61])=[N:43][N:44]([CH:46]3[CH2:47][CH2:48][N:49]([C:52]([O:54][C:55]([CH3:57])([CH3:58])[CH3:56])=[O:53])[CH2:50][CH2:51]3)[CH:45]=2)[CH:13]=[N:12][C:11]=1[N:25]([C:26]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:32])[C:33]([O:35][C:36]([CH3:39])([CH3:37])[CH3:38])=[O:34]

参加物

7

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 67388042Tert-butyl 4-[4-bromo-3-(methoxymethyl)pyrazol-1-yl]piperidine-1-carboxylateHCID 67388208Tert-butyl N-[3-(1,3-benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]-N-tert-butoxycarbonyl-carbamate

生成物 1

HCID 67388447Tert-butyl 4-[4-[5-(1,3-benzoxazol-2-yl)-6-(bis(tert-butoxycarbonyl)amino)-3-pyridyl]-3-(methoxymethyl)pyrazol-1-yl]piperidine-1-carboxylate収率 74.5%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

A mixture of tert-butyl N-[3-(1,3-benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridyl]-N-tert-butoxycarbonyl-carbamate (808 mg), tert-butyl 4-(4-bromo-3-(methoxymethyl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (439 mg), trisdibenzylideneacetone dipalladium (53.7 mg), dicyclohexyl-[2-(2,6-dimethoxyphenyl)phenyl]phosphane (48.2 mgl) and potassium phosphate (0.233 g) in a mixture of dioxane (14 ml) and water (350 μl) was degassed. The resulting suspension was stirred at 120° C. for 3 hours under argon. After the mixture was cooled to room temperature the solvent was concentrated, ethyl acetate (80 ml) and water (20 ml) were added. The organic layer was washed with brine, dried over magnesium sulphate, filtered and evaporated under reduce pressure. The crude product was purified by flash chromatography on silica gel eluting with 30 to 80% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford tert-butyl 4-[4-[5-(1,3-benzoxazol-2-yl)-6-(bis(tert-butoxycarbonyl)amino)-3-pyridyl]-3-(methoxymethyl)pyrazol-1-yl]piperidine-1-carboxylate (616 mg). The N-tert-butoxycarbonyl groups on the resultant product were removed by conventional treatment with hydrogen chloride in isopropanol to afford 3-(1,3-benzoxazol-2-yl)-5-[3-(methoxymethyl)-1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine (300 mg).

後処理

  1. customwas degassed
  2. temperatureAfter the mixture was cooled to room temperature the solvent
  3. concentrationwas concentrated
  4. additionethyl acetate (80 ml) and water (20 ml) were added
  5. washThe organic layer was washed with brine
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product was purified by flash chromatography on silica gel eluting with 30 to 80% ethyl acetate in petroleum ether
  10. customThe solvent was evaporated to dryness

出典と根拠

ORDレコード
ord-8bc4c3c426154d98b83d6fee9974de98
出典データセット
uspto-grants-2011_09
特許番号
US08017611B2

反応ノート

読み込み中…