Acetic Acid → (3-methyl-1-((9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-6-morpholino-9H-purin-8-yl)methyl)pyrrolidin-3-yl)(pyrrolidin-1-yl)methanone

HRID 1945939노트

반응식

HRID 1945939 반응식
[CH3:1][N:2]1[C:10]([CH:11]=O)=[N:9][C:8]2[C:3]1=[N:4][C:5]([N:19]1[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[N:21]=[C:20]1[CH3:28])=[N:6][C:7]=2[N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.[CH3:29][C:30]1([C:35]([N:37]2[CH2:41][CH2:40][CH2:39][CH2:38]2)=[O:36])[CH2:34][CH2:33][NH:32][CH2:31]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.CO>[CH3:29][C:30]1([C:35]([N:37]2[CH2:41][CH2:40][CH2:39][CH2:38]2)=[O:36])[CH2:34][CH2:33][N:32]([CH2:11][C:10]2[N:2]([CH3:1])[C:3]3[C:8]([N:9]=2)=[C:7]([N:13]2[CH2:14][CH2:15][O:16][CH2:17][CH2:18]2)[N:6]=[C:5]([N:19]2[C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=4[N:21]=[C:20]2[CH3:28])[N:4]=3)[CH2:31]1

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 596054202-(2-methylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehydeHCID 63140531(3-Methylpyrrolidin-3-yl)(pyrrolidin-1-yl)methanone

생성물 1

HCID 59606072(3-methyl-1-((9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-6-morpholino-9H-purin-8-yl)methyl)pyrrolidin-3-yl)(pyrrolidin-1-yl)methanone수율 76%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 887Methanol용매

실험 절차

A mixture of 9-methyl-2-(2-methylbenzoimidazol-1-yl)-6-morpholin-4-yl-9H-purine-8-carbaldehyde (100 mg, 0.26 mmol), (3-methylpyrrolidin-3-yl)pyrrolidin-1-ylmethanone (58 mg, 0.32 mmol), trimethoxyorthoformate (0.29 mL, 2.65 mmol) and acetic acid (15 μL, 0.26 mmol) in DCE (5 mL) was stirred at room temperature for 1 hour then sodium triacetoxyborohydride (90 mg, 0.42 mmol) was added. The reaction mixture was stirred at room temperature for 18 hours then diluted with MeOH and loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was washed with MeOH and the desired product was eluted with 2M NH3 in MeOH. The solvents were removed and the residue was subjected to flash chromatography (Si—PCC, 0-20% MeOH in EtOAc) to give 396 as a white solid (107 mg, 76%). LCMS (Method G): RT 6.69 min; [M+H]+ 544. 1H NMR (400 MHz, CHCl3-d): δ 8.12-8.07 (m, 1 H); 7.74-7.70 (m, 1 H); 7.30-7.26 (m, 2 H); 4.35 (m, 4 H); 3.90 (s, 3 H); 3.87 (t, J=4.75 Hz, 5 H); 3.49 (m, 5 H); 2.96 (s, 3 H); 2.64 (s, 2 H); 2.46-2.37 (m, 2 H); 1.89 (m, 4 H); 1.81 (m, 2 H); 1.41 (s, 3 H).

후처리

  1. stirringThe reaction mixture was stirred at room temperature for 18 hours
  2. washThe cartridge was washed with MeOH
  3. washthe desired product was eluted with 2M NH3 in MeOH
  4. customThe solvents were removed

출처 및 근거

ORD 기록
ord-ab12984b34d84587acfb93ac320ce99b
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08394796B2

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