tert-Butanol → [7-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]carbamic acid tert-butyl ester

HRID 2113790Notes

Reaction equation

HRID 2113790 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[N:10]1[CH2:15][CH2:14][CH2:13][C:12]2=[C:16](C(O)=O)[N:17]([CH3:19])[N:18]=[C:11]12.[C:23]([OH:27])([CH3:26])([CH3:25])[CH3:24].C([N:30]([CH2:33]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:42])C=CC=CC=1>C(OCC)(=O)C.CCCCCC>[C:23]([O:27][C:33](=[O:42])[NH:30][C:16]1[N:17]([CH3:19])[N:18]=[C:11]2[C:12]=1[CH2:13][CH2:14][CH2:15][N:10]2[C:3]1[C:4]([CH3:9])=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=1[Cl:1])([CH3:26])([CH3:25])[CH3:24]

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 221362637-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine-3-carboxylic acid

Product 1

HCID 23527225[7-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

A 159 mg sample of 7-(2-chloro-4,6-dimethylphenyl)-2-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine-3-carboxylic acid (5-1) was combined with 2.5 mL of t-butanol and 140 μL of triethylamine was added. To this mixture was added 129 μL of diphenylphosphoryl azide and the reaction mixture was heated to 85° C. for 2 h. After cooling to room temperature, the reaction mixture was dissolved in ethyl acetate and washed sequentially with 1M aqueous sodium bisulfate, aqueous sodium bicarbonate, water, and brine. The ethyl acetate solution was dried with magnesium sulfate and concentrated. The crude product was flash chromatographed on silica gel eluting with an acetone/hexane gradient to afford a solid residue which was slurried in a small amount of boiling hexane. After the mixture cooled to room temperature, the solids were collected by filtration to provide 71 mg of 5-3: mp 171.4-175.7° C.

Workup

  1. additionwas added
  2. temperatureAfter cooling to room temperature
  3. washwashed sequentially with 1M aqueous sodium bisulfate, aqueous sodium bicarbonate, water, and brine
  4. dry with materialThe ethyl acetate solution was dried with magnesium sulfate
  5. concentrationconcentrated
  6. customchromatographed on silica gel eluting with an acetone/hexane gradient
  7. customto afford a solid residue which
  8. temperatureAfter the mixture cooled to room temperature
  9. filtrationthe solids were collected by filtration

Sources & evidence

ORD record
ord-9bb584343c804fe8aaf3b8980d7dd1b2
Source dataset
uspto-grants-2008_10
Patent number
US07432283B2

Reaction notes

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