Sodium Chloride → HCID 178451638, compound

HRID 2215676Notes

Reaction equation

HRID 2215676 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6](C)[C:5](C)=[CH:4][C:3]=1[NH:10][C:11]([C:13]1[NH:14][N:15]=[C:16]2[C:21]=1[CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]2)=[O:12].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.NC1C=C(C)C(C)=CC=1N.[Na+].[Cl-]>CN(C=O)C.C([O-])(O)=O.[Na+].ClCCl>[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:10][C:11]([C:13]1[NH:14][N:15]=[C:16]2[C:21]=1[CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]2)=[O:12]

Participants

9

Reactant 5

HCID 5234Sodium ChlorideHCID 766354,5-Dimethyl-1,2-phenylenediamineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178428585HCID 178428585, compound

Product 1

HCID 178451638HCID 178451638, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

tert-Butyl 3-(2-amino-4,5-dimethylphenylcarbamoyl)-2,4,5,7-tetrahydro-pyrazolo[3,4-c]pyridine-6-carboxylate can be prepared in the following way: 8.5 g of HBTU and also 2.9 g of diisopropylethylamine are added, at ambient temperature, to a solution of 3 g of (tert-butyl 2,4,5,7-tetrahydropyrazolo-[3,4-c]pyridine-6-carboxylate)-3-carboxylic acid in 50 ml of anhydrous DMF. After twenty minutes' stirring at ambient temperature, 3.06 g of 4,5-diamino-o-xylene are added. After stirring at ambient temperature for 60 hours, the reaction medium is diluted in 3 l of an aqueous NaHCO3 solution at pH greater than 7, containing 20 g of NaCl. The aqueous phase is extracted three times with 1 l of ethyl acetate, and the combined organic phases are then dried over magnesium sulphate and concentrated under reduced pressure. The crude residue obtained is taken up in 150 ml of dichloromethane and the insoluble material is removed by filtration through sintered glass. The filtrate is then concentrated under reduced pressure and purified by chromatography on silica (20–45 μm Amicon) with a gradient of from 50 to 100% of ethyl acetate in cyclohexane. The fractions containing the desired product are combined and concentrated under reduced pressure. 4.37 g of tert-butyl 3-(2-aminophenylcarbamoyl)-2,4,5,7-tetrahydro-pyrazolo[3,4-c]pyridine-6-carboxylate are thus obtained in the form of a beige powder, the characteristics of which are as follows:

Workup

  1. stirringAfter stirring at ambient temperature for 60 hours
  2. extractionThe aqueous phase is extracted three times with 1 l of ethyl acetate
  3. dry with materialthe combined organic phases are then dried over magnesium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe crude residue obtained
  6. customthe insoluble material is removed by filtration through sintered glass
  7. concentrationThe filtrate is then concentrated under reduced pressure
  8. custompurified by chromatography on silica (20–45 μm Amicon) with a gradient of from 50 to 100% of ethyl acetate in cyclohexane
  9. additionThe fractions containing the desired product
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-52fd8b2c60ff48bf8a76254c4cff2dc4
Source dataset
uspto-grants-2006_09
Patent number
US07109340B2

Reaction notes

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