Dimethylcarbamoyl Chloride → 3-(5,6-dimethyl-1H-benzoimidazol-2-yl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid isopropylamide

HRID 2182368Notes

Reaction equation

HRID 2182368 reaction equation
[CH3:1][C:2]1[C:19]([CH3:20])=[CH:18][C:5]2[NH:6][C:7]([C:9]3[C:13]4[CH2:14][NH:15][CH2:16][CH2:17][C:12]=4[NH:11][N:10]=3)=[N:8][C:4]=2[CH:3]=1.[CH:21]([N:24]([CH:27](C)C)CC)([CH3:23])[CH3:22].CN(C)C(Cl)=[O:33]>CN(C)C=O>[CH:21]([NH:24][C:27]([N:15]1[CH2:16][CH2:17][C:12]2[NH:11][N:10]=[C:9]([C:7]3[NH:6][C:5]4[CH:18]=[C:19]([CH3:20])[C:2]([CH3:1])=[CH:3][C:4]=4[N:8]=3)[C:13]=2[CH2:14]1)=[O:33])([CH3:23])[CH3:22]

Participants

5

Reactant 3

HCID 6598Dimethylcarbamoyl ChlorideHCID 81531DiisopropylethylamineHCID 1358045913-(5,6-dimethyl-1H-benzoimidazol-2-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 1359003323-(5,6-dimethyl-1H-benzoimidazol-2-yl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid isopropylamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3-(5,6-dimethyl-1H-benzoimidazol-2-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine [0.150 g, Example 251(a)] in dimethyl formamide (4 ml) was treated with diisopropylethylamine (0.54 ml) and then with dimethyl carbamyl chloride (0.122 ml). After stirring for 1 hour the reaction mixture was quenched by the addition of methanol (0.1 ml) and then diluted with ethyl acetate. This mixture was washed five times with brine and then evaporated. The residue was treated with tetrahydrofuran (9 ml) and methanol (3 ml) and the resulting solution was then treated with potassium hydroxide (50 mg). This mixture was stirred for 1 hour, then acidified by addition of hydrochloric acid (1M) and then extracted three times with ethyl acetate. The aqueous layer was basified by addition of sodium carbonate and the resulting suspension was filtered, then washed with water, then dried in air and then azeotroped with toluene to yield 3-(5,6-dimethyl-1H-benzoimidazol-2-yl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid isopropylamide as a pale brown solid. MS: 339 (M+H)+. HPLC (METHOD F1): RT=8.67 minutes. (b) Cyclopropyl-[3-(5,6-dimethyl-1H-benzoimidazol-2-yl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-methanone

Workup

  1. customwas quenched by the addition of methanol (0.1 ml)
  2. additiondiluted with ethyl acetate
  3. washThis mixture was washed five times with brine
  4. customevaporated
  5. additionThe residue was treated with tetrahydrofuran (9 ml) and methanol (3 ml)
  6. additionthe resulting solution was then treated with potassium hydroxide (50 mg)
  7. stirringThis mixture was stirred for 1 hour
  8. additionacidified by addition of hydrochloric acid (1M)
  9. extractionextracted three times with ethyl acetate
  10. additionThe aqueous layer was basified by addition of sodium carbonate
  11. filtrationthe resulting suspension was filtered
  12. washwashed with water
  13. customdried in air
  14. customazeotroped with toluene

Sources & evidence

ORD record
ord-f68fd8cc211141fea0ab53c763a902db
Source dataset
uspto-grants-2005_05
Patent number
US06897208B2

Reaction notes

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