Diethyl cyanophosphonate → tert-Butyl cis-5-{[(1-cyclobutyl-1H-indazol-3-yl)carbonyl]amino}-2-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]piperidine-1-carboxylate

HRID 602460ノート

反応式

HRID 602460 の反応式
[CH:1]1([N:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7]([C:14]([OH:16])=O)=[N:6]2)[CH2:4][CH2:3][CH2:2]1.[NH2:17][C@H:18]1[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@@H:21]([CH2:31][C:32]2([OH:38])[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)[CH2:20][CH2:19]1.C(P(=O)(OCC)OCC)#N.C(N(CC)C(C)C)(C)C.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH:1]1([N:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7]([C:14]([NH:17][C@H:18]3[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:29])([CH3:30])[CH3:28])=[O:25])[C@@H:21]([CH2:31][C:32]4([OH:38])[CH2:33][CH2:34][O:35][CH2:36][CH2:37]4)[CH2:20][CH2:19]3)=[O:16])=[N:6]2)[CH2:2][CH2:3][CH2:4]1

参加物

7

反応物 5

HCID 76257Diethyl cyanophosphonateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 214787871-Cyclobutyl-1H-indazole-3-carboxylic acidHCID 67269815tert-Butyl cis-5-amino-2-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]piperidine-1-carboxylate

生成物 1

HCID 67270199tert-Butyl cis-5-{[(1-cyclobutyl-1H-indazol-3-yl)carbonyl]amino}-2-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]piperidine-1-carboxylate収率 35%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

The mixture of 1-cyclobutyl-1H-indazole-3-carboxylic acid (135 mg, 0.63 mmol, step 2 of Example 4), tert-butyl cis-5-amino-2-[(4-hydroxytetrahydro-2H-pyran-4-yl)methyl]piperidine-1-carboxylate (197 mg, 6.27 mmol, step 5 of Example 2), diethyl cyanophosphonate (0.13 mL, 0.75 mmol), and N,N-diisopropylethylamine (0.16 mL, 0.94 mmol) in N,N-dimethylformamide (10 mL) was stirred at room temperature for 12 h. Then the mixture was poured onto aqueous saturated sodium hydrogencarbonate (100 mL), and the aqueous layer was extracted with ethyl acetate/toluene (3:1, 100 mL×3). The combined organic layer was concentrated under reduced pressure. The residue was chromatographed on a column of silica gel eluting with ethyl acetate/n-hexane (1:2) to give 112 mg (35%) of the title compound as a pale yellow amorphous.

後処理

  1. extractionthe aqueous layer was extracted with ethyl acetate/toluene (3:1, 100 mL×3)
  2. concentrationThe combined organic layer was concentrated under reduced pressure
  3. customThe residue was chromatographed on a column of silica gel eluting with ethyl acetate/n-hexane (1:2)

出典と根拠

ORDレコード
ord-877a7abe0d75412c8172f96051ab30bf
出典データセット
uspto-grants-2011_03
特許番号
US07906532B2

反応ノート

読み込み中…