Dichloromethane → 7-cyclopentyl-2-(5-(8-(1-hydroxypropan-2-yl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-ylamino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

HRID 627361ノート

反応式

HRID 627361 の反応式
[CH:1]12[NH:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:9]([C:11]1[CH:12]=[CH:13][C:14]([NH:17][C:18]3[N:19]=[CH:20][C:21]4[CH:26]=[C:25]([C:27]([N:29]([CH3:31])[CH3:30])=[O:28])[N:24]([CH:32]5[CH2:36][CH2:35][CH2:34][CH2:33]5)[C:22]=4[N:23]=3)=[N:15][CH:16]=1)=[O:10])[CH2:2]2.C(O[BH-]([O:46][C:47](=O)[CH3:48])OC(=O)C)(=O)C.[Na+].Cl[CH2:52]Cl>>[CH:32]1([N:24]2[C:22]3[N:23]=[C:18]([NH:17][C:14]4[CH:13]=[CH:12][C:11]([C:9]([N:3]5[CH2:4][CH:5]6[N:8]([CH:48]([CH3:52])[CH2:47][OH:46])[CH:1]([CH2:7][CH2:6]6)[CH2:2]5)=[O:10])=[CH:16][N:15]=4)[N:19]=[CH:20][C:21]=3[CH:26]=[C:25]2[C:27]([N:29]([CH3:31])[CH3:30])=[O:28])[CH2:33][CH2:34][CH2:35][CH2:36]1

参加物

4

反応物 3

HCID 6344Dichloromethane2 回HCID 5049666Sodium triacetoxyborohydrideHCID 533786742-(5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-ylamino)-7-cyclopentyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

生成物 1

HCID 673559947-cyclopentyl-2-(5-(8-(1-hydroxypropan-2-yl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-ylamino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide収率 33%

実験手順

To a solution of 2-(5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-ylamino)-7-cyclopentyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (105 mg, 0.22 mmol) in dichloromethane (2 ml) 1-hydroxypropan-2-one (2 ml) was added and the resulting reaction mixture was stirred for 1H at room temperature. Sodium triacetoxyborohydride was added and the reaction mixture was stirred at room temperature overnight. When TLC/LCMS show completion the reaction mixture is diluted with dichloromethane, washed with sat NaHCO3 (2×) and brine. The combined aqueous layers back extracted with dichloromethane and the combined organic layers are dried over sodium sulfate, filtered, concentrated and purified by column chromatography (0-20% methanol/dichloromethane) which gave 7-cyclopentyl-2-(5-(8-(1-hydroxypropan-2-yl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-ylamino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (39 mg, 33% yield). 1H NMR (400 MHz, CDCl3) δ ppm 9.07 (s, 1H) 8.85 (s, 1H) 8.57 (d, J=9.09 Hz, 1H) 8.45 (s, 1H) 7.78 (dd, J=8.59, 2.53 Hz, 1H) 6.48 (s, 1H) 4.81 (dq, J=9.09, 8.93 Hz, 1H) 4.48 (br. s., 1H) 3.75-3.30 (m, 6H) 3.23-3.00 (m, 7H) 2.69-2.50 (m, 3H) 2.16-1.97 (m, 5H) 1.97-1.66 (m, 6H) 1.10 (d, J=6.06 Hz, 3H); HR-MS (m/z MH+) 547.32 RT 2.54 min.

後処理

  1. customthe resulting reaction mixture
  2. stirringthe reaction mixture was stirred at room temperature overnight
  3. washwashed
  4. extractionThe combined aqueous layers back extracted with dichloromethane
  5. dry with materialthe combined organic layers are dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by column chromatography (0-20% methanol/dichloromethane) which

出典と根拠

ORDレコード
ord-5df575ef69b94acb98fcbe879f86b519
出典データセット
uspto-grants-2016_04
特許番号
US09309252B2

反応ノート

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