Sodium cyanoborohydride → HCID 178501323, compound

HRID 511588Notes

Reaction equation

HRID 511588 reaction equation
O=[C:2]1[CH2:5][CH:4]([C:6]([O:8][CH3:9])=[O:7])[CH2:3]1.[NH2:10][CH2:11][C@@H:12]1[C@H:16]2[O:17][C:18]([CH3:21])([CH3:20])[O:19][C@H:15]2[C@H:14]([N:22]2[CH:30]=[N:29][C:28]3[C:23]2=[N:24][CH:25]=[N:26][C:27]=3[NH2:31])[O:13]1.[BH3-]C#N.[Na+]>CO>[NH2:31][C:27]1[N:26]=[CH:25][N:24]=[C:23]2[C:28]=1[N:29]=[CH:30][N:22]2[C@H:14]1[C@@H:15]2[O:19][C:18]([CH3:20])([CH3:21])[O:17][C@@H:16]2[C@@H:12]([CH2:11][NH:10][C@H:2]2[CH2:5][C@H:4]([C:6]([O:8][CH3:9])=[O:7])[CH2:3]2)[O:13]1

Participants

5

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 113012155'-Amino-5'-deoxy-2',3'-O-(1-methylethylidene)-adenosineHCID 13992367Methyl 3-oxocyclobutane-1-carboxylate

Product 1

HCID 178501323HCID 178501323, compoundYield 41.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of methyl 3-oxocyclobutanecarboxylate (4.60 g, 35.94 mmol), 9-((3aR,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purin-6-amine (11.0 g, 35.94 mmol) and Ti(iPrO)4 (4.0 g, 14.08 mmol) in MeOH (80 mL) was stirred at 45° C. for 2 h, then NaCNBH3 (4.5 g, 71.87 mmol) was added. The reaction was stirred at RT overnight. The reaction was quenched with aq. sat. NaHCO3 (40 mL) and filtered, extracted with DCM (80 mL×3), dried over Na2SO4 and concentrated. The residue was purified by preparative-HPLC to obtain the title compound (6.2 g, Yield 41%). 1H NMR (500 MHz, CDCl3): δH 8.38-8.34 (m, 1H), 7.90 (s, 1H), 5.98 (d, J=3.0 Hz, 1H), 5.75 (br s, 2H), 5.48-5.46 (m, 1H), 5.03-5.01 (m, 1H), 4.35-4.33 (m, 1H), 3.69-3.66 (m, 3H), 3.50-3.17 (m, 1H), 3.05-2.73 (m, 3H), 2.48-2.44 (m, 2H), 1.95-1.91 (m, 2H), 1.62 (s, 3H), 1.39 (s, 3H) ppm; ESI-MS (m/z): 419.2[M+1]+.

Workup

  1. customThe reaction was quenched with aq. sat. NaHCO3 (40 mL)
  2. filtrationfiltered
  3. extractionextracted with DCM (80 mL×3)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by preparative-HPLC

Sources & evidence

ORD record
ord-69c83961200d4f1d93b4e4fef1c240a3
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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