Diisopropylethylamine → tert-butyl [(3S)-1-({[1-methyl-5-(tritylamino)-1H-pyrazol-4-yl]amino)carbonyl)-3-pyrrolidinyl]carbamate

HRID 1247824Notes

Reaction equation

HRID 1247824 reaction equation
[CH3:1][N:2]1[C:6]([NH:7][C:8]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[C:5]([NH:27][C:28](=O)[O:29]C2C=CC=CC=2)[CH:4]=[N:3]1.[NH:37]1[CH2:41][CH2:40][C@H:39]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[CH2:38]1.C(N(C(C)C)C(C)C)C>C(Cl)Cl>[CH3:1][N:2]1[C:6]([NH:7][C:8]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[C:5]([NH:27][C:28]([N:37]2[CH2:41][CH2:40][C@H:39]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:46])([CH3:48])[CH3:47])[CH2:38]2)=[O:29])[CH:4]=[N:3]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 21904567Phenyl [1-methyl-5-(tritylamino)pyrazol-4-yl]carbamate

Product 1

HCID 69778830tert-butyl [(3S)-1-({[1-methyl-5-(tritylamino)-1H-pyrazol-4-yl]amino)carbonyl)-3-pyrrolidinyl]carbamateYield 59.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of phenyl [1-methyl-5-(tritylamino)-1H-pyrazol-4-yl]carbamate (950 mg) and tert-butyl (3S)-3-pyrrolidinylcarbamate (560 mg) in methylene chloride (20 ml) was added N-ethyldiisopropylamine (390 mg), and the mixture was stirred under reflux for 23 hours. The reaction mixture was washed successively with 10% aqueous citric acid solution, brine and saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with 4% methanol/chloroform to give tert-butyl [(3S)-1-({[1-methyl-5-(tritylamino)-1H-pyrazol-4-yl]amino}carbonyl)-3-pyrrolidinyl]carbamate (680 mg) as a solid.

Workup

  1. temperatureunder reflux for 23 hours
  2. washThe reaction mixture was washed successively with 10% aqueous citric acid solution, brine and saturated aqueous sodium hydrogen carbonate solution
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography on silica gel eluting with 4% methanol/chloroform

Sources & evidence

ORD record
ord-e6f0ce36048e4bb0af194ccca41838e1
Source dataset
uspto-grants-2006_10
Patent number
US07129232B2

Reaction notes

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