Sodium cyanoborohydride → HCID 178501323, compound

HRID 2040628Notes

Reaction equation

HRID 2040628 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-1852da50ffd54380aeabb9be73c16392
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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