4-Methylmorpholine → HCID 178448373, compound

HRID 1068878Notes

Reaction equation

HRID 1068878 reaction equation
C[N:2]1[CH2:7][CH2:6][O:5]CC1.Cl[C:9]([O:11][CH2:12][CH:13]([CH3:15])[CH3:14])=[O:10].[NH2:16][C:17]1[C:25]2[C:20](=[N:21][CH:22]=[N:23][C:24]=2[NH:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([Cl:33])[CH:28]=2)[NH:19][N:18]=1>C1COCC1>[CH2:12]([O:11][C:9]([NH:2][C@H:7]([C:6]([NH:16][C:17]1[C:25]2[C:20](=[N:21][CH:22]=[N:23][C:24]=2[NH:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([Cl:33])[CH:28]=2)[NH:19][N:18]=1)=[O:5])[CH:27]([CH3:32])[CH3:28])=[O:10])[C:13]1[CH:15]=[CH:20][CH:25]=[CH:24][CH:14]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 178509242HCID 178509242, compound

Product 1

HCID 178448373HCID 178448373, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Analogously to Example 5, 386 mg (1.53 mmol) of N-benzyloxycarbonyl-(D,L)valine in 3.2 ml of THF and 337 μl (3.07 mmol) of NMM are activated with 219 μl (1.68 mmol) of isobutyl chloroformate and then reacted with 400 mg (1.53 mmol) of 3-amino-4-(3-chloro-phenylamino)-1H-pyrazolo[3,4-d]pyrimidine (see Step 1.6). The reaction mixture is concentrated by evaporation; ethyl acetate is added to the residue and the ethyl acetate suspension is washed with 2N HCl solution, sat. NaHCO3 solution and brine and finally the insoluble crude product is filtered off. Crystallization from a hot mixture of 1.1 ml of DMSO and 10 ml of ethanol yields rac.-3-([N-benzyloxycarbonyl-valyl]-amino)-4-(3-chlorophenylamino)-1H-pyrazolo[3,4-d]pyrimidine; HPLC:tRet(grad20-100/20)=1 4.9; FAB-MS: (M+H)+=494.

Workup

  1. concentrationThe reaction mixture is concentrated by evaporation
  2. additionethyl acetate is added to the residue
  3. washthe ethyl acetate suspension is washed with 2N HCl solution, sat. NaHCO3 solution and brine
  4. filtrationfinally the insoluble crude product is filtered off
  5. customCrystallization
  6. additionfrom a hot mixture of 1.1 ml of DMSO and 10 ml of ethanol

Sources & evidence

ORD record
ord-39901dd3ce8b4193ba5101356d091ad0
Source dataset
uspto-grants-2001_06
Patent number
US06251911B1

Reaction notes

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