Triethylamine → HCID 91224811, compound

HRID 1093187Notes

Reaction equation

HRID 1093187 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]([CH:25]([CH3:27])[CH3:26])[N:23]=[CH:24][C:10]=13)[CH2:2]2.C(N(CC)CC)C.Cl[C:36](Cl)([O:38][C:39](=O)[O:40]C(Cl)(Cl)Cl)Cl.N(C1C=CC(C2N=C3N(C(C)C)N=CC3=C(N3CC4OC(CC4)C3)N=2)=CC=1)=C=O>ClCCl.CO>[CH3:36][O:38][C:39](=[O:40])[NH:19][C:18]1[CH:20]=[CH:21][C:15]([C:13]2[N:12]=[C:11]3[N:22]([CH:25]([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 8471TriethylamineHCID 94429TriphosgeneHCID 66589012HCID 66589012, compoundHCID 87063194HCID 87063194, compound

Product 1

HCID 91224811HCID 91224811, compoundYield 88.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)aniline (0.027 g, 0.07 mmol) in dichloromethane (2 mL) was treated with triethylamine (0.028 mL), followed by a solution of triphosgene (0.011 g, 0.04 mmol) in dichloromethane (1 mL). After the passage of 10 minutes, the appropriate nucleophile—in the case, methanol (excess)—was added to the 3-(6-(4-isocyanatophenyl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane (“isocyanate”) mixture. After 10 minutes, 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 over 35 minutes to provide methyl{4-[1-isopropyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}carbamate (15 mg, 48%). MS (ES+): 423.2 (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 over 35 minutes

Sources & evidence

ORD record
ord-40910d238373451ab60c278fd8d4130d
Source dataset
uspto-grants-2012_03
Patent number
US08129371B2

Reaction notes

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