Water → HCID 68982784, compound

HRID 1516279Notes

Reaction equation

HRID 1516279 reaction equation
[C:1]([O:9][CH2:10][C@@H:11]1[C:15]([O:17][C:18](=[O:20])[CH3:19])([CH3:16])[C@:14]([F:22])([CH3:21])[CH:13]([N:23]2[CH:31]=[N:30][C:29]3[C:24]2=[N:25][CH:26]=[N:27][C:28]=3Cl)[O:12]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N12CCC[N:40]=[C:39]1[CH2:38][CH2:37][CH2:36]CC2.Cl.NCC1CC1.O>C(O)C>[C:1]([O:9][CH2:10][C@@H:11]1[C:15]([O:17][C:18](=[O:20])[CH3:19])([CH3:16])[C@:14]([F:22])([CH3:21])[CH:13]([N:23]2[CH:31]=[N:30][C:29]3[C:24]2=[N:25][CH:26]=[N:27][C:28]=3[NH:40][CH2:39][CH:38]2[CH2:37][CH2:36]2)[O:12]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 81671(Cyclopropylmethyl)ammonium chlorideHCID 86634317HCID 86634317, compound

Product 1

HCID 68982784HCID 68982784, compoundYield 72.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of ((2R,4R)-3-acetoxy-5-(6-chloro-9H-purin-9-yl)-4-fluoro-3,4-dimethyl-tetrahydrofuran-2-yl)methyl benzoate (about 0.30 g, 0.64 mmol) in ethanol (about 5 ml) was added 1,8-Diazabicyclo[5.4.0]undec-7-ene (about 0.14 ml, 0.97 mmol) and aminomethyl cyclopropane hydrochloride (about 0.14 g, 1.2 mmol) at room temperature and refluxed for about 30 minutes. Completion of the reaction monitored by thin-layer chromatography, water added to the reaction mixture and the aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with water, brine and dried over sodium sulphate. Concentration under reduced pressure and purification by silica gel column chromatography using 5% methanol in dichloromethane as eluent furnished title compound (0.23 g) as a colorless solid. Yield: 67%; 1H NMR (300 MHz, CDCl3): δ 8.39 (s, 1H), 8.06-8.04 (m, 2H), 7.99 (d, 1H, J=3.6 Hz), 7.60-7.55 (m, 1H), 7.47-7.42 (m, 2H), 6.54 (d, 1H, J=23.1 Hz), 5.93 (bs, 1H), 4.84-4.78 (m, 2H), 4.49-4.42 (m, 1H), 3.49 (bs, 2H), 2.16 (s, 3H), 1.89 (d, 3H, J=2.4 Hz), 1.44 (d, 3H, J=23.1 Hz), 1.19-1.08 (m, 1H), 0.59-0.55 (m, 2H), 0.34-0.31 (m, 2H); ES Mass: [M+1]+ 498 (100%), [M+Na] 520 (45%); HPLC: 96%.

Workup

  1. temperaturerefluxed for about 30 minutes
  2. additionadded to the reaction mixture
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washthe combined organic layers were washed with water, brine
  5. dry with materialdried over sodium sulphate
  6. concentrationConcentration
  7. customunder reduced pressure and purification by silica gel column chromatography

Sources & evidence

ORD record
ord-6ccd771533fe47f6b751fb14448a8c75
Source dataset
uspto-grants-2012_07
Patent number
US08227431B2

Reaction notes

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