Acetic Acid → 3-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)-1-(tetrahydro-2H-pyran-4-yl)azetidin-3-ol

HRID 1946135노트

반응식

HRID 1946135 반응식
[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([C:18]4([OH:22])[CH2:21][NH:20][CH2:19]4)[N:14]3[CH3:17])=[C:10]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[N:9]=2)[C:6]2[CH:29]=[CH:30][CH:31]=[CH:32][C:5]=2[N:4]=1)[CH3:2].[O:33]1[CH2:38][CH2:37][C:36](=O)[CH2:35][CH2:34]1.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([C:18]4([OH:22])[CH2:21][N:20]([CH:36]5[CH2:37][CH2:38][O:33][CH2:34][CH2:35]5)[CH2:19]4)[N:14]3[CH3:17])=[C:10]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[N:9]=2)[C:6]2[CH:29]=[CH:30][CH:31]=[CH:32][C:5]=2[N:4]=1)[CH3:2]

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 121599Tetrahydro-4H-pyran-4-one2회HCID 5049666Sodium triacetoxyborohydride2회HCID 596060743-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]azetidine-3-ol

생성물 1

HCID 596056283-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)-1-(tetrahydro-2H-pyran-4-yl)azetidin-3-ol

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 6344Dichloromethane용매

실험 절차

A mixture of 3-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-azetidin-3-ol (490 mg, 1.13 mmol), tetrahydropyran-4-one (158 mg, 1.58 mmol), AcOH (130 μL, 2.25 mmol) and 4 Å powdered molecular sieves (640 mg) in DCE (15 mL) was allowed to stir for 5 min before the addition of sodium triacetoxyborohydride (478 mg, 2.25 mmol) portion wise over 5 min. The resulting mixture was allowed to stir for 4 h at r.t before the addition of further tetrahydropyran-4-one (158 mg, 1.58 mmol) and sodium triacetoxyborohydride (478 mg, 2.25 mmol). The mixture was stirred for 2 h then diluted with DCM and washed with 1M NaOH. The organic phase was dried (phase separator) and concentrated in vacuo. The resulting oil was purified by column chromatography (Si—PCC, 2M NH3/MeOH:DCM, 0-15%) then (C18, MeOH:H2O, 7.5-25%). The resulting residue was loaded onto an Isolute® SCX-2 cartridge which was washed with DCM and MeOH and the product eluted with 2M NH3/MeOH affording 720 as a white foam (309 mg, 53%). LCMS (method I): RT 2.40 min, [M+H]+ 519.3. 1H NMR (MeOD, 400 MHz): δ 8.01-8.00 (1 H, m), 7.66-7.61 (1 H, m), 7.28-7.27 (2 H, m), 4.38 (4 H, s), 4.24 (2 H, d, J=8.76 Hz), 3.97-3.94 (2 H, m), 3.85 (7 H, s), 3.56 (2 H, d, J=8.75 Hz), 3.31-3.31 (5 H, m), 2.54-2.52 (1 H, m), 1.83-1.73 (2 H, m), 1.38 (5 H, t, J=7.49 Hz)

후처리

  1. washwashed with 1M NaOH
  2. customThe organic phase was dried (phase separator)
  3. concentrationconcentrated in vacuo
  4. customThe resulting oil was purified by column chromatography (Si—PCC, 2M NH3/MeOH:DCM, 0-15%)
  5. washwas washed with DCM and MeOH
  6. washthe product eluted with 2M NH3/MeOH affording 720 as a white foam (309 mg, 53%)
  7. customRT 2.40 min, [M+H]+ 519.3

출처 및 근거

ORD 기록
ord-5c55aa45a1404865a5f8e72d458e5244
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08394796B2

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