Water → 4-Amino-2-[1-(2,3-difluorobenzyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-5,5-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one

HRID 570534Notes

Reaction equation

HRID 570534 reaction equation
[F:1][C:2]1[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([CH3:14])=[N:12][CH:13]=[C:8]2[C:7]([C:15](=[NH:17])[NH2:16])=[N:6]1.[C:23]([CH:25]([C:33]#[N:34])[C:26]([CH3:32])([CH3:31])[C:27](OC)=[O:28])#[N:24].CC(C)([O-])C.[K+].O>C(O)(C)(C)C>[NH2:24][C:23]1[C:25]2[C:26]([CH3:32])([CH3:31])[C:27](=[O:28])[NH:34][C:33]=2[N:17]=[C:15]([C:7]2[C:8]3[C:9](=[N:10][C:11]([CH3:14])=[N:12][CH:13]=3)[N:5]([CH2:4][C:3]3[CH:18]=[CH:19][CH:20]=[C:21]([F:22])[C:2]=3[F:1])[N:6]=2)[N:16]=1

Participants

6

Reactant 4

HCID 962WaterHCID 23665647Potassium tert-butoxideHCID 86657403Methyl 3,3-dicyano-2,2-dimethylpropanoateHCID 866921001-(2,3-Difluorobenzyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboximidamide

Product 1

HCID 866921014-Amino-2-[1-(2,3-difluorobenzyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-5,5-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent2×

Procedure

400 mg (1.11 mmol) of 1-(2,3-difluorobenzyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboximidamide were admixed with 3 ml of tert-butanol, 277 mg (1.33 mmol) of methyl 3,3-dicyano-2,2-dimethylpropanoate dissolved in 2 ml of tert-butanol and 175 mg (1.56 mmol) of potassium tert-butoxide, and the mixture was heated to reflux for 24 h. A little water was added and the reaction solution was purified by means of preparative HPLC (eluent: acetonitrile/water, gradient 30:70→95:5). The product-containing fractions were concentrated and the residue was stirred with water/isopropanol. The solids were filtered off and purified again by means of preparative HPLC (eluent: acetonitrile/water with 0.1% hydrochloric acid, gradient 20:80→100:0). 170 mg (35% of theory) of the target compound were obtained.

Workup

  1. temperatureto reflux for 24 h
  2. customthe reaction solution was purified by means of preparative HPLC (eluent: acetonitrile/water, gradient 30:70→95:5)
  3. concentrationThe product-containing fractions were concentrated
  4. filtrationThe solids were filtered off
  5. custompurified again by means of preparative HPLC (eluent: acetonitrile/water with 0.1% hydrochloric acid, gradient 20:80→100:0)
  6. custom170 mg (35% of theory) of the target compound were obtained

Sources & evidence

ORD record
ord-94fb613f552f47408b5c8216f4ab7eee
Source dataset
uspto-grants-2015_05
Patent number
US09023849B2

Reaction notes

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