Pyridine, hydrofluoride (1:1) → HCID 59671337, compound

HRID 1747601Notes

Reaction equation

HRID 1747601 reaction equation
[S:1](=[O:38])(=[O:37])([O:3][CH2:4][C@@H:5]1[CH2:9][C@@H:8]([O:10][C:11]2[CH:16]=[C:15]([NH:17][C@@H:18]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH2:20][C@@H:19]3[O:27][CH3:28])[N:14]=[CH:13][N:12]=2)[CH2:7][C@@H:6]1[O:29][Si](C(C)(C)C)(C)C)[NH2:2].F.N1C=CC=CC=1>N1C=CC=CC=1.C1COCC1>[S:1](=[O:38])(=[O:37])([O:3][CH2:4][C@@H:5]1[CH2:9][C@@H:8]([O:10][C:11]2[CH:16]=[C:15]([NH:17][C@@H:18]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH2:20][C@@H:19]3[O:27][CH3:28])[N:14]=[CH:13][N:12]=2)[CH2:7][C@@H:6]1[OH:29])[NH2:2]

Participants

5

Reactant 2

HCID 64774Pyridine, hydrofluoride (1:1)2×HCID 86618710HCID 86618710, compound

Product 1

HCID 59671337HCID 59671337, compoundYield 52.5%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of {(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 sulfamate (0.239 g, 0.000423 mol) in pyridine (3.44 mL) and THF (3.44 mL) was added pyridine hydrofluoride (0.953 mL, 0.0106 mol) dropwise. After stirring the reaction for 2 hours, an additional amount of pyridine hydrofluoride (0.50 mL, 0.0055 mol) was added. After 2.75 hours the reaction was quenched by slow dropwise addition of saturated aqueous NaHCO3 and extracted with EtOAc (4×). The combined organic phases were dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (0 to 10% MeOH/CH2Cl2) and then by preparative plate chromatography (EtOAc) to obtain 100 mg (52%) of the title compound. 1H NMR (CD3OD, 400 MHz) δ: 8.15 (s, 1H), 7.24-7.15 (m, 4H), 5.98 (s, 1H), 5.34 (bs, 1H), 4.41-4.38 (m, 1H), 4.32 (dd, 1H, J=7.5, 9.7 Hz), 4.24-4.20 (m, 1H), 4.17 (dd, 1H, J=7.3, 9.8 Hz), 3.35 (s, 3H), 3.13-3.00 (m, 3H), 2.57-2.48 (m, 1H), 2.31-2.25 (m, 1H) 2.12-1.93 (m, 4H) ppm. LC/MS: Rt=1.33 min, ES+ 451 (FA standard).

Workup

  1. customthe reaction for 2 hours
  2. customAfter 2.75 hours the reaction was quenched by slow dropwise addition of saturated aqueous NaHCO3
  3. extractionextracted with EtOAc (4×)
  4. dry with materialThe combined organic phases were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (0 to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-f570bc2f6dd94fc58bf6d59384f77519
Source dataset
uspto-grants-2015_10
Patent number
US09150525B2

Reaction notes

Loading…