Triethylamine → (1R,4R)-2-Oxa-5-azabicyclo[2.2.1]heptan-5-yl((R)-1-(2-(2-cyclopropylpyrimidin-4-yl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)methanone

HRID 931266ノート

反応式

HRID 931266 の反応式
[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[NH:27][C:13]4=[N:14][C:15]([N:18]5[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24](O)=[O:25])[CH2:19]5)=[CH:16][CH:17]=[C:12]4[N:11]=3)[CH:7]=[CH:6][N:5]=2)[CH2:3][CH2:2]1.C(N=C=NCCCN(C)C)C.[OH:39][C:40]1[C:48]2[N:47]=NN[C:44]=2[CH:43]=[CH:42]C=1.C(N(CC)CC)C.[C@@H]12O[C@@H](CC1)CNC2>CN(C)C=O.CN(C)C1C=CN=CC=1>[C@@H:43]12[CH2:44][C@@H:48]([N:47]([C:24]([C@@H:20]3[CH2:21][CH2:22][CH2:23][N:18]([C:15]4[N:14]=[C:13]5[NH:27][C:10]([C:8]6[CH:7]=[CH:6][N:5]=[C:4]([CH:1]7[CH2:3][CH2:2]7)[N:9]=6)=[N:11][C:12]5=[CH:17][CH:16]=4)[CH2:19]3)=[O:25])[CH2:42]1)[CH2:40][O:39]2

参加物

8

反応物 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 46831336(1R,5S)-8-oxa-3-azabicyclo[3.2.1]octaneHCID 178418300HCID 178418300、化合物HCID 178525786HCID 178525786、化合物

生成物 1

HCID 178521012(1R,4R)-2-Oxa-5-azabicyclo[2.2.1]heptan-5-yl((R)-1-(2-(2-cyclopropylpyrimidin-4-yl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)methanone収率 10.5%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of (R)-1-(2-(2-cyclopropylpyrimidin-4-yl)-3H-imidazo[4,5-b]pyridin-5-yl)piperidine-3-carboxylic acid (70 mg, 0.192 mmol) in N,N-dimethylformamide (10 mL) were added 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDCl) (73.2 mg, 0.383 mmol), hydroxybenzotriazole (52 mg, 0.383 mmol), triethylamine (58.2 mg, 0.575 mmol), (1R,5S)-8-oxa-3-azabicyclo[3.2.1]octane (186 mg, 1.64 mmol) and 4-dimethylaminopyridine (3 mg) at room temperature. The reaction mixture was stirred for 18 h, poured into ice water, extracted with ethyl acetate, washed with cold water and concentrated. The crude was purified via preparative TLC (3% methanol in dichloromethane) to afford the title compound (9 mg). MS (ES+) (M+H) 446.3; LCMS retention time 1.816 min (Method F)

後処理

  1. extractionextracted with ethyl acetate
  2. washwashed with cold water
  3. concentrationconcentrated
  4. customThe crude was purified via preparative TLC (3% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-12165dc850eb4088ab70699b91a70412
出典データセット
uspto-grants-2016_03
特許番号
US09296745B2

反応ノート

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