Methylamine → HCID 25261558, compound

HRID 1093219Notes

Reaction equation

HRID 1093219 reaction equation
[CH2:1]([N:8]1[C:12]2=[N:13][C:14]([C:25]3[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=3)=[N:15][C:16]([N:17]3[CH2:23][CH:22]4[O:24][CH:19]([CH2:20][CH2:21]4)[CH2:18]3)=[C:11]2[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.CN.C(N1C2=NC(C3C=C[C:73]([N:76]=[C:77]=[O:78])=CC=3)=NC(N3CC4OC(CC4)C3)=C2C=N1)C1C=CC=CC=1>ClCCl.O1CCCC1>[CH2:1]([N:8]1[C:12]2=[N:13][C:14]([C:25]3[CH:26]=[CH:27][C:28]([NH:29][C:77]([NH:76][CH3:73])=[O:78])=[CH:30][CH:31]=3)=[N:15][C:16]([N:17]3[CH2:18][CH:19]4[O:24][CH:22]([CH2:21][CH2:20]4)[CH2:23]3)=[C:11]2[CH:10]=[N:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6329MethylamineHCID 94429TriphosgeneHCID 66589133HCID 66589133, compoundHCID 86629379HCID 86629379, compound

Product 1

HCID 25261558HCID 25261558, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-(1-benzyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)aniline (22 mg, 0.05 mmol) in a mixture of dichloromethane (3 mL) and tetrahydrofuran (2 mL) was treated with triphosgene (8 mg, 0.03 mmol) as a solution in dichloromethane (1 mL). After the passage of 5 minutes, the appropriate nucleophile—in the case, 2.0 M methylamine solution in tetrahydrofuran (1 mL)—was added to the 3-(1-benzyl-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 1-{4-[1-benzyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}-3-methylurea. MS (ES+): 470.0 (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-0cbcb304faa64583a05703bf30503a47
Source dataset
uspto-grants-2012_03
Patent number
US08129371B2

Reaction notes

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