Tetrahydrofuran → tert-butyl (aminosulfonyl)({(1S,2S,4R)-2-hydroxy-4-[(6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}pyrimidin-4-yl)oxy]cyclopentyl}methyl)carbamate

HRID 1677957Notes

Reaction equation

HRID 1677957 reaction equation
[NH2:1][S:2]([N:5]([CH2:13][C@@H:14]1[CH2:18][C@@H:17]([O:19][C:20]2[CH:25]=[C:24]([NH:26][C@@H:27]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36][CH3:37])[N:23]=[CH:22][N:21]=2)[CH2:16][C@@H:15]1[O:38][Si](C(C)(C)C)(C)C)[C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])(=[O:4])=[O:3].C1COCC1.F.N1C=CC=CC=1>N1C=CC=CC=1>[NH2:1][S:2]([N:5]([CH2:13][C@@H:14]1[CH2:18][C@@H:17]([O:19][C:20]2[CH:25]=[C:24]([NH:26][C@@H:27]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36][CH3:37])[N:23]=[CH:22][N:21]=2)[CH2:16][C@@H:15]1[OH:38])[C:6](=[O:12])[O:7][C:8]([CH3:10])([CH3:11])[CH3:9])(=[O:3])=[O:4]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 64774Pyridine, hydrofluoride (1:1)2×HCID 66797969tert-butyl (aminosulfonyl)({(1S,2S,4R)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-[(6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}-pyrimidin-4-yl)oxy]cyclopentyl}methyl)carbamate

Product 1

HCID 66797857tert-butyl (aminosulfonyl)({(1S,2S,4R)-2-hydroxy-4-[(6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}pyrimidin-4-yl)oxy]cyclopentyl}methyl)carbamate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of tert-butyl (aminosulfonyl)({(1S,2S,4R)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-[(6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}-pyrimidin-4-yl)oxy]cyclopentyl}methyl)carbamate (331.5 mg, 0.0004094 mol) in THF (1.84 mL, 0.0228 mol) and pyridine (1.84 mL) at 0° C. was added pyridine hydrofluoride (0.25 mL, 0.0028 mol) dropwise. The mixture was allowed to slowly warm to 23° C. and stirred for 19 hours. To the reaction was added pyridine hydrofluoride (0.25 mL, 0.0028 mol) and the mixture was stirred an additional 6 hours. The reaction was quenched by the dropwise addition of saturated aqueous NaHCO3. The mixture was partitioned with additional saturated aqueous NaHCO3 and EtOAc, separated, and the aqueous was extracted with EtOAc (2×) and CH2Cl2 (2×). The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (30 to 70% EtOAc/hexanes) to collect 34.5 mg (15%) of the title compound. LC/MS: Rt=1.64 min, ES+ 550 (FA standard).

Workup

  1. stirringthe mixture was stirred an additional 6 hours
  2. customThe reaction was quenched by the dropwise addition of saturated aqueous NaHCO3
  3. customThe mixture was partitioned with additional saturated aqueous NaHCO3 and EtOAc
  4. customseparated
  5. extractionthe aqueous was extracted with EtOAc (2×) and CH2Cl2 (2×)
  6. washThe combined organics were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography (30 to 70% EtOAc/hexanes)
  11. customto collect 34.5 mg (15%) of the title compound

Sources & evidence

ORD record
ord-caf90332cc4b451aa4d21ff9f19e0d39
Source dataset
uspto-grants-2011_08
Patent number
US08008307B2

Reaction notes

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