Sodium cyanoborohydride → methyl3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutanecarboxylate

HRID 2040621노트

반응식

HRID 2040621 반응식
O=[C:2]1[CH2:5][CH:4]([C:6]([O:8][CH3:9])=[O:7])[CH2:3]1.[CH3:10][C:11]1([CH3:32])[O:15][C@@H:14]2[C@@H:16]([CH2:29][NH:30][CH3:31])[O:17][C@@H:18]([N:19]3[CH:27]=[N:26][C:25]4[C:20]3=[N:21][CH:22]=[N:23][C:24]=4[NH2:28])[C@@H:13]2[O:12]1.[BH3-]C#N.[Na+]>CO>[CH3:9][O:8][C:6]([CH:4]1[CH2:5][CH:2]([N:30]([CH2:29][C@@H:16]2[C@@H:14]3[C@@H:13]([O:12][C:11]([CH3:32])([CH3:10])[O:15]3)[C@H:18]([N:19]3[CH:27]=[N:26][C:25]4[C:20]3=[N:21][CH:22]=[N:23][C:24]=4[NH2:28])[O:17]2)[CH3:31])[CH2:3]1)=[O:7]

참가 물질

5

반응물 3

HCID 5003444Sodium cyanoborohydrideHCID 110236419-((3aR,4R,6R,6aR)-2,2-Dimethyl-6-((methylamino)methyl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purin-6-amineHCID 13992367Methyl 3-oxocyclobutane-1-carboxylate

생성물 1

HCID 67774297methyl3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutanecarboxylate수율 63%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

A solution of methyl 3-oxocyclobutanecarboxylate (1.28 g crude), 9-((3aR,4R,6R,6aR)-2,2-dimethyl-6-((methylamino)methyl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purin-6-amine (2.0 g, 6.25 mmol) (Townsend et al Org Lett 2009, 11, 2976-2679) and Ti(iPrO)4 (1.78 g, 6.25 mmol) in MeOH (50 mL) was stirred at 45° C. for 2 h, then NaCNBH3 (0.79 g, 12.50 mmol) was added. The reaction was stirred at RT overnight. The reaction was quenched with aq. sat. NaHCO3 (40 mL), filtered, extracted with DCM (40 mL×3), dried over Na2SO4 and concentrated. The residue was purified by SGC (DCM:MeOH=12:1) to obtain title compound (1.7 g, Yield 63%). 1H NMR (500 MHz, MeOD): δH 8.28-8.27 (m, 1H), 8.21 (s, 1H), 6.20-6.18 (m, 1H), 5.52 (dd, J=1.5, 6.0 Hz, 1H), 5.00 (dd, J=3.0, 6.0 Hz, 1H), 5.33 (brs, 1H), 3.65-3.63 (m, 3H), 2.77-2.55 (m, 4H), 2.19-2.11 (m, 5H), 2.00-1.82 (m, 2H), 1.59 (s, 3H), 1.38 (s, 3H) ppm; ESI-MS (m/z): 433.2 [M+1]+.

후처리

  1. customThe reaction was quenched with aq. sat. NaHCO3 (40 mL)
  2. filtrationfiltered
  3. extractionextracted with DCM (40 mL×3)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by SGC (DCM:MeOH=12:1)

출처 및 근거

ORD 기록
ord-253a5a0232da40b18987b3e2d086258d
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08580762B2

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