Diiodomethane → 2-[1-(Cyclopentylmethyl)-5-fluoro-1H-pyrazolo[3,4-b]pyridin-3-yl]-4-iodo-5,5-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one

HRID 1529165Notes

Reaction equation

HRID 1529165 reaction equation
I[CH2:2][I:3].N(OCCC(C)C)=O.NC1[C:14]2[C:37]([CH3:39])([CH3:38])[C:36](=[O:40])[NH:35][C:15]=2[N:16]=[C:17]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25]([F:28])[CH:26]=3)[N:21]([CH2:29][CH:30]3[CH2:34][CH2:33][CH2:32][CH2:31]3)[N:20]=2)[N:18]=1>>[CH:30]1([CH2:29][N:21]2[C:22]3=[N:23][CH:24]=[C:25]([F:28])[CH:26]=[C:27]3[C:19]([C:17]3[N:18]=[C:2]([I:3])[C:14]4[C:37]([CH3:38])([CH3:39])[C:36](=[O:40])[NH:35][C:15]=4[N:16]=3)=[N:20]2)[CH2:34][CH2:33][CH2:32][CH2:31]1

Participants

4

Reactant 3

HCID 6346DiiodomethaneHCID 8053Isoamyl NitriteHCID 709796024-Amino-2-[1-(cyclopentyl methyl)-5-fluoro-1H-pyrazolo[3,4-b]pyridin-3-yl]-5,5-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one

Product 1

HCID 867151712-[1-(Cyclopentylmethyl)-5-fluoro-1H-pyrazolo[3,4-b]pyridin-3-yl]-4-iodo-5,5-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one

Conditions

Temperature
85 °C

Procedure

40.549 g (151.398 mmol) of diiodomethane and 4.420 g (37.738 mmol) of isopentyl nitrite were added to 711 mg (1.799 mmol) of 4-amino-2-[1-(cyclopentylmethyl)-5-fluoro-1H-pyrazolo[3,4-b]pyridin-3-yl]-5,5-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one. The mixture was stirred at 85° C. for 8 h. After cooling, the mixture was filtered, and the filtrate was diluted with cyclohexane and sucked through silica gel. The silica gel was washed with cyclohexane and the product was eluted with dichloromethane/methanol (v/v=50:2). The collected fractions were concentrated on a rotary evaporator, taken up in 20 ml of ethyl acetate and 5 ml of isopropanol, filtered and concentrated again. The residue was triturated with 5 ml of isopropanol. The solid was filtered off with suction and dried under high vacuum. This gave 230 mg (purity 92%, 23% of theory) of the target compound.

Workup

  1. temperatureAfter cooling
  2. filtrationthe mixture was filtered
  3. additionthe filtrate was diluted with cyclohexane
  4. washThe silica gel was washed with cyclohexane
  5. washthe product was eluted with dichloromethane/methanol (v/v=50:2)
  6. concentrationThe collected fractions were concentrated on a rotary evaporator
  7. filtration5 ml of isopropanol, filtered
  8. concentrationconcentrated again
  9. customThe residue was triturated with 5 ml of isopropanol
  10. filtrationThe solid was filtered off with suction
  11. customdried under high vacuum

Sources & evidence

ORD record
ord-05e698dc80b44fb5b5713c63144a6c70
Source dataset
uspto-grants-2015_07
Patent number
US09090610B2

Reaction notes

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