p-Toluenesulfonic acid monohydrate → HCID 69262583, compound

HRID 888158Notes

Reaction equation

HRID 888158 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][C:16]([CH3:19])([CH3:18])[C:15]2[C:10](=[CH:11][C:12]([NH:20][C:21]([C:23]3[C:24]([NH2:29])=[N:25][CH:26]=[CH:27][CH:28]=3)=[O:22])=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:30]1[C:34]2=[N:35][CH:36]=[CH:37][CH:38]=[C:33]2[C:32]([CH:39]=O)=[CH:31]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[BH4-].[Na+]>C1(C)C=CC=CC=1.CO>[C:1]([O:5][C:6]([N:8]1[CH2:17][C:16]([CH3:19])([CH3:18])[C:15]2[C:10](=[CH:11][C:12]([NH:20][C:21]([C:23]3[C:24]([NH:29][CH2:39][C:32]4[C:33]5[C:34](=[N:35][CH:36]=[CH:37][CH:38]=5)[NH:30][CH:31]=4)=[N:25][CH:26]=[CH:27][CH:28]=3)=[O:22])=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 521998p-Toluenesulfonic acid monohydrateHCID 4311764Sodium borohydrideHCID 53728121H-Pyrrolo[2,3-b]pyridine-3-carbaldehydeHCID 69264418HCID 69264418, compound

Product 1

HCID 69262583HCID 69262583, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Procedure

A mixture of 7-[(2-amino-pyridine-3-carbonyl)-amino]-4,4-dimethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (1.0 g, 2.5 mmol), 1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde (730 mg, 5.0 mmol), and p-toluenesulfonic acid monohydrate (48 mg, 0.25 mmol) in 50 mL of anhydrous toluene was stirred at reflux for 1 h. After being cooled to RT, the mixture was diluted with 2 mL of MeOH and NaBH4 (475 mg, 12.5 mmol) was added, and the mixture was stirred at RT for 30 min. The reaction was quenched with MeOH, and the volatiles were removed under reduced pressure. The residue was taken up in water, AcOH was added to bring pH to 4, and the mixture was extracted with EtOAc. The combined organic portions were washed with brine, dried over MgSO4, filtered, and condensed. The residue was purified by flash column chromatography to give 4,4-dimethyl-7-({2-[(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-amino]-pyridine-3-carbonyl}-amino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester. MS (ES+): 527.2 (M+H)+. Calc'd for C30H34N6O3 526.27.

Workup

  1. temperatureat reflux for 1 h
  2. additionwas added
  3. stirringthe mixture was stirred at RT for 30 min
  4. customThe reaction was quenched with MeOH
  5. customthe volatiles were removed under reduced pressure
  6. additionAcOH was added
  7. extractionthe mixture was extracted with EtOAc
  8. washThe combined organic portions were washed with brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customcondensed
  12. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-56ef9f0178f64d83a9c8be32b731405f
Source dataset
uspto-grants-2012_08
Patent number
US08247556B2

Reaction notes

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