Hydrochloric Acid → 1-{4-[4-(9-Oxa-3,7-diazabicyclo[3.3.1]non-3-yl)-1-(2,2,2-trifluoroethyl)-1h-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-4-ylurea

HRID 1093201Notes

Reaction equation

HRID 1093201 reaction equation
Cl.[N:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:47])[NH:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[N:22]=[C:21]4[N:23]([CH2:26][C:27]([F:30])([F:29])[F:28])[N:24]=[CH:25][C:20]4=[C:19]([N:31]4[CH2:38][CH:37]5[O:39][CH:33]([CH2:34][N:35](C(OC(C)(C)C)=O)[CH2:36]5)[CH2:32]4)[N:18]=3)=[CH:13][CH:12]=2)=[CH:4][CH:3]=1.Cl>ClCCl.CO.O1CCOCC1>[CH:33]12[O:39][CH:37]([CH2:36][NH:35][CH2:34]1)[CH2:38][N:31]([C:19]1[N:18]=[C:17]([C:14]3[CH:13]=[CH:12][C:11]([NH:10][C:9]([NH:8][C:5]4[CH:4]=[CH:3][N:2]=[CH:7][CH:6]=4)=[O:47])=[CH:16][CH:15]=3)[N:22]=[C:21]3[N:23]([CH2:26][C:27]([F:29])([F:30])[F:28])[N:24]=[CH:25][C:20]=13)[CH2:32]2

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 66588973Tert-butyl 7-(6-(4-(3-pyridin-4-ylureido)phenyl)-1-(2,2,2-trifluoroethyl)-1h-pyrazolo[3,4-d]pyrimidin-4-yl)-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate.hydrochloride

Product 1

HCID 574246031-{4-[4-(9-Oxa-3,7-diazabicyclo[3.3.1]non-3-yl)-1-(2,2,2-trifluoroethyl)-1h-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-4-ylurea

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

Tert-butyl 7-(6-(4-(3-pyridin-4-ylureido)phenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate.hydrochloride (256 mg, 0.38 mmol) was dissolved in dichloromethane (20 mL) with the aid of a minimum volume of methanol. The solution was treated with 4 N hydrogen chloride in dioxane (2 mL), which caused the precipitation of a white solid within 10 minutes. The solid was collected by Buchner filtration, washed with methanol, and dried under house vacuum. A portion of the crude solid (assumed dihydrochloride) was purified by reverse-phase high performance liquid chromatography using a Phenomenex Prodigy 21 mm×250 mm column, running a gradient elution of 5% acetonitrile/95% of 0.1% aqueous trifluoroacetic acid to 65% acetonitrile to provide 1-{4-[4-(9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-pyridin-4-ylurea.2TFA (22 mg). MS (ES+): 540.2 (M+H)+

Workup

  1. customthe precipitation of a white solid within 10 minutes
  2. filtrationThe solid was collected by Buchner filtration
  3. washwashed with methanol
  4. customdried under house vacuum
  5. customA portion of the crude solid (assumed dihydrochloride) was purified by reverse-phase high performance liquid chromatography
  6. washa gradient elution of 5% acetonitrile/95% of 0.1% aqueous trifluoroacetic acid to 65% acetonitrile

Sources & evidence

ORD record
ord-0fdf995b6cf3424c9633d3f7549eadd7
Source dataset
uspto-grants-2012_03
Patent number
US08129371B2

Reaction notes

Loading…