Methanol → HCID 91359122, compound

HRID 1093220Notes

Reaction equation

HRID 1093220 reaction equation
[CH:1]12[O:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:9]1[N:14]=[C:13]([C:15]3[CH:21]=[CH:20][C:18]([NH2:19])=[CH:17][CH:16]=3)[N:12]=[C:11]3[N:22]([C:25]([CH3:28])([CH3:27])[CH3:26])[N:23]=[CH:24][C:10]=13)[CH2:2]2.Cl[C:30](Cl)([O:32][C:33](=O)[O:34]C(Cl)(Cl)Cl)Cl.CO.C(N1C2=NC(C3C=CC(N=C=O)=CC=3)=NC(N3CC4OC(CC4)C3)=C2C=N1)(C)(C)C>ClCCl.O1CCCC1>[CH3:30][O:32][C:33](=[O:34])[NH:19][C:18]1[CH:20]=[CH:21][C:15]([C:13]2[N:12]=[C:11]3[N:22]([C:25]([CH3:28])([CH3:27])[CH3:26])[N:23]=[CH:24][C:10]3=[C:9]([N:3]3[CH2:2][CH:1]4[O:8][CH:5]([CH2:6][CH2:7]4)[CH2:4]3)[N:14]=2)=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 94429TriphosgeneHCID 66589030HCID 66589030, compoundHCID 87063290HCID 87063290, compound

Product 1

HCID 91359122HCID 91359122, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-tert-butyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)aniline (65 mg, 0.17 mmol) in a mixture of dichloromethane (2 mL) and tetrahydrofuran (2 mL) was treated with triphosgene (26 mg, 0.09 mmol) as a solution in dichloromethane (1 mL). After the passage of 10 minutes, the appropriate nucleophile—in the case, methanol (excess)—was added to the 3-(1-tert-butyl-6-(4-isocyanatophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane (“isocyanate”) mixture. The reaction mixture was concentrated to dryness under reduced pressure. The residue 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 100% acetonitrile to provide methyl{4-[1-tert-butyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate. MS (ES+): 437.2 (M+H)+

Workup

  1. concentrationThe reaction mixture was concentrated to dryness under reduced pressure
  2. customThe residue was purified by reverse-phase high performance liquid chromatography
  3. washa gradient elution of 5% acetonitrile/95% of 0.1% aqueous trifluoroacetic acid to 100% acetonitrile

Sources & evidence

ORD record
ord-876f7097469543fcbdf8bcade35725b6
Source dataset
uspto-grants-2012_03
Patent number
US08129371B2

Reaction notes

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