HCID 86614252, compound → HCID 58944608, compound

HRID 222178Notes

Reaction equation

HRID 222178 reaction equation
[S:1](=[O:33])(=[O:32])([O:3][CH2:4][C@@H:5]1[CH2:9][C@@H:8]([N:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([NH:19][CH2:20][CH:21]4[CH2:23][CH2:22]4)[C:13]=3[CH:12]=[CH:11]2)[CH2:7][C@@H:6]1[O:24][Si](C(C)(C)C)(C)C)[NH2:2]>C1COCC1.N1C=CC=CC=1.F.N1C=CC=CC=1>[S:1](=[O:32])(=[O:33])([O:3][CH2:4][C@@H:5]1[CH2:9][C@@H:8]([N:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([NH:19][CH2:20][CH:21]4[CH2:22][CH2:23]4)[C:13]=3[CH:12]=[CH:11]2)[CH2:7][C@@H:6]1[OH:24])[NH2:2]

Participants

5

Reactant 1

HCID 86614252HCID 86614252, compound

Product 1

HCID 58944608HCID 58944608, compoundYield 4.4%

Reagents, catalysts & solvents 3

HCID 64774Pyridine, hydrofluoride (1:1)CatalystHCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

((1S,2S,4R)-2-{[tert-Butyl(dimethyl)silyl]oxy}-4-{4-[(cyclopropylmethyl)amino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentyl)methyl sulfamate (88.0 mg, 0.178 mmol) was dissolved in THF (1.00 mL) and pyridine (3.00 mL). Pyridine hydrofluoride (12 drops) was added and the reaction was stirred for 3 h. The reaction was quenched using saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with EtOAc (3×10 mL), and the combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with 5% MeOH in DCM. The compound was re-purified via silica gel chromatography eluting with 10% MeOH in DCM to afford the title compound (3.00 mg, 4.4%). 1H NMR (400 MHz, CD3OD, δ): 8.05 (s, 1H), 7.15 (d, J=3.6 Hz, 1H), 6.59 (d, J=3.6 Hz, 1H), 5.45-5.32 (m, 1H), 4.56 (br s, 1H), 4.45 (br s, 1H), 4.33 (dd, J=7.6, 7.6 Hz, 1H), 4.15 (dd, J=7.4, 7.4 Hz, 1H), 3.34 (d, J=6.9 Hz, 2H), 2.83-2.68 (m, 1H), 2.35-2.08 (m, 3H), 2.05-1.93 (m, 1H), 1.33-1.03 (m, 3H), 0.93-0.77 (m, 1H) ppm. LC/MS: Rt=0.85 min, ES+ 382 (FA standard).

Workup

  1. customThe reaction was quenched
  2. extractionThe aqueous layer was extracted with EtOAc (3×10 mL)
  3. dry with materialthe combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with 5% MeOH in DCM
  8. customThe compound was re-purified via silica gel chromatography
  9. washeluting with 10% MeOH in DCM

Sources & evidence

ORD record
ord-385a2e143299475e8ad80f3cc43dc40d
Source dataset
uspto-grants-2012_06
Patent number
US08207177B2

Reaction notes

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