Benzyl carbamate → benzyl(4-(hydroxymethyl)-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)carbamate

HRID 588204Notes

Reaction equation

HRID 588204 reaction equation
CC(C)([O-])C.[Na+].Cl[C:8]1[N:13]=[C:12]([CH2:14][OH:15])[C:11]2[C:16]([O:38][CH3:39])=[N:17][N:18]([C:19]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:10]=2[CH:9]=1.[C:40](=[O:50])([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[NH2:41]>C1COCC1>[CH2:43]([O:42][C:40](=[O:50])[NH:41][C:8]1[N:13]=[C:12]([CH2:14][OH:15])[C:11]2[C:16]([O:38][CH3:39])=[N:17][N:18]([C:19]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:10]=2[CH:9]=1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

5

Reactant 3

HCID 12136Benzyl carbamateHCID 23676156Sodium t-butoxideHCID 118271763(6-chloro-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-4-yl)methanol

Product 1

HCID 118371771benzyl(4-(hydroxymethyl)-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)carbamateYield 57.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A 20 mL scintillation vial was charged with sodium tert-butoxide (105 mg, 1.097 mmol), (6-chloro-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-4-yl)methanol (35B, 250 mg, 0.548 mmol), benzyl carbamate (124 mg, 0.822 mmol) and BrettPhos-Pd-G3 (24.85 mg, 0.027 mmol). THF (5 ml) was added, the vial flushed with argon, capped and the contents heated to 50° C. with stirring for 10 h. The mixture was cooled, diluted with ethyl acetate (10 mL), washed with aqueous sodium hydrogen carbonate (saturated, 2×20 mL), dried (MgSO4), filtered and the solvent evaporated under reduced pressure. The resulting residue was purified by column chromatography on silica gel ISCO; 24 g prepacked, eluting with EtOAc/hexanes to afford benzyl(4-(hydroxymethyl)-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)carbamate (181 mg, 0.317 mmol, 57.8% yield) as a white solid. MS: [M+H]+ m/z 571.

Workup

  1. customthe vial flushed with argon
  2. customcapped
  3. temperatureThe mixture was cooled
  4. additiondiluted with ethyl acetate (10 mL)
  5. washwashed with aqueous sodium hydrogen carbonate (saturated, 2×20 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent evaporated under reduced pressure
  9. customThe resulting residue was purified by column chromatography on silica gel ISCO
  10. washeluting with EtOAc/hexanes

Sources & evidence

ORD record
ord-b97f7221584d4a9aa580dc2e11508b4e
Source dataset
uspto-grants-2016_01
Patent number
US09226922B2

Reaction notes

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