Pyridine → HCID 58944580, compound

HRID 222212Notes

Reaction equation

HRID 222212 reaction equation
[S:1](=[O:39])(=[O:38])([O:3][CH2:4][CH2:5][C@@H:6]1[CH2:10][C@@H:9]([N:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([NH:20][C@@H:21]4[C:29]5[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=5)[CH2:23][CH2:22]4)[C:14]=3[CH:13]=[CH:12]2)[CH2:8][C@@H:7]1[O:30][Si](C(C)(C)C)(C)C)[NH2:2].N1C=CC=CC=1.O1CCCC1.F.N1C=CC=CC=1>>[S:1](=[O:39])(=[O:38])([O:3][CH2:4][CH2:5][C@@H:6]1[CH2:10][C@@H:9]([N:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([NH:20][C@@H:21]4[C:29]5[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=5)[CH2:23][CH2:22]4)[C:14]=3[CH:13]=[CH:12]2)[CH2:8][C@@H:7]1[OH:30])[NH2:2]

Participants

5

Reactant 4

HCID 1049PyridineHCID 8028TetrahydrofuranHCID 64774Pyridine, hydrofluoride (1:1)3×HCID 58944703HCID 58944703, compound

Product 1

HCID 58944580HCID 58944580, compoundYield 12.9%

Conditions

Temperature
0 °C

Procedure

2-((1S,2S,4R)-2-{[tert-Butyl(dimethyl)silyl]oxy}-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentyl)ethyl sulfamate (0.0442 g, 0.0773 mmol) was dissolved in pyridine (0.344 mL, 4.25 mmol) and tetrahydrofuran (0.345 mL, 4.25 mmol). The solution was cooled to 0° C. Pyridine hydrofluoride (0.500 mL, 5.55 mmol) was added dropwise. The solution was warmed to room temperature. After one hour, pyridine hydrofluoride (0.500 mL, 5.55 mmol) was added. After two hours, pyridine hydrofluoride (0.500 mL, 5.55 mmol) was added. The solution was stirred for 24 h. The reaction was quenched with dropwise addition of saturated sodium bicarbonate, and the mixture was extracted with EtOAc. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with 0 to 5% MeOH in EtOAc, to give the title compound (0.005 g, 0.01 mmol). 1H NMR (CD3OD, 400 MHz, δ): 8.17 (s, 1H), 7.28-7.12 (m, 5H) 6.67 (d, J=3.61 Hz 1H) 5.58 (t, J=7.44, 7.44 Hz 1H), 5.48-5.40 (m, 1H), 4.40-4.35 (m, 1H), 4.28-4.17 (m, 2H), 3.10-3.02 (m, 1H), 2.98-2.88 (m, 1H), 2.68-2.47 (m, 1H), 2.57-2.47 (m, 1H), 2.38-1.98 (m, 5H), 1.89-1.80 (m, 1H) ppm. LC/MS: Rt=1.25 min, ES+ 458 (FA standard).

Workup

  1. temperatureThe solution was warmed to room temperature
  2. waitAfter two hours
  3. customThe reaction was quenched with dropwise addition of saturated sodium bicarbonate
  4. extractionthe mixture was extracted with EtOAc
  5. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with 0 to 5% MeOH in EtOAc

Sources & evidence

ORD record
ord-3a99c28d641c468c92525312f307c26e
Source dataset
uspto-grants-2012_06
Patent number
US08207177B2

Reaction notes

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