Methylamine → HCID 25262026, compound

HRID 1093177Notes

Reaction equation

HRID 1093177 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]4[CH2:30][CH2:29][N:28]([CH2:31][C:32]([F:35])([F:34])[F:33])[CH2:27][CH2:26]4)[N:23]=[CH:24][C:10]=13)[CH2:2]2.[CH2:36]([N:38]([CH2:41]C)CC)C.ClC(Cl)([O:46]C(=O)OC(Cl)(Cl)Cl)Cl.CN>ClCCl.O1CCCC1>[CH3:36][NH:38][C:41]([NH:19][C:18]1[CH:20]=[CH:21][C:15]([C:13]2[N:12]=[C:11]3[N:22]([CH:25]4[CH2:26][CH2:27][N:28]([CH2:31][C:32]([F:34])([F:35])[F:33])[CH2:29][CH2:30]4)[N:23]=[CH:24][C:10]3=[C:9]([N:3]3[CH2:4][CH:5]4[O:8][CH:1]([CH2:7][CH2:6]4)[CH2:2]3)[N:14]=2)=[CH:16][CH:17]=1)=[O:46]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 8471TriethylamineHCID 94429TriphosgeneHCID 66589022HCID 66589022, compound

Product 1

HCID 25262026HCID 25262026, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)aniline (110 mg, 0.22 mmol) in a mixture of dichloromethane (10 mL) and tetrahydrofuran (10 mL) was treated with triethylamine (0.10 mL), followed by triphosgene (100 mg, 0.34 mmol). After the passage of five minutes, 2.0 M methylamine solution in tetrahydrofuran (10 mL) was added. The mixture was concentrated to dryness under reduced pressure. The resultant residue was purified via reverse-phase high performance liquid chromatography using a Phenomenex Prodigy 21 mm×250 mm column, running a gradient elution of 10% acetonitrile/90% of 0.1% aqueous trifluoroacetic acid to 95% acetonitrile. After the concentration of fractions under reduced pressure, 1-methyl-3-(4-{4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenyl)urea was obtained. MS (ES+): 545.2 (M+H)+

Workup

  1. concentrationThe mixture was concentrated to dryness under reduced pressure
  2. customThe resultant residue was purified via reverse-phase high performance liquid chromatography
  3. washa gradient elution of 10% acetonitrile/90% of 0.1% aqueous trifluoroacetic acid to 95% acetonitrile

Sources & evidence

ORD record
ord-e187c879861546a498f5b99241f95765
Source dataset
uspto-grants-2012_03
Patent number
US08129371B2

Reaction notes

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