Methylamine → HCID 57424695, compound

HRID 1093227Notes

Reaction equation

HRID 1093227 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]3[N:14]([CH2:17][C:18]([F:21])([F:20])[F:19])[N:15]=[CH:16][C:11]3=[C:10]([N:22]3[CH:27]4[CH2:28][N:29]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:30][CH:23]3[CH2:24][O:25][CH2:26]4)[N:9]=2)=[CH:4][CH:3]=1.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.CN.[N:52]([C:55]1C=CC(C2N=C3N(CC(F)(F)F)N=CC3=C(N3C4CN(C(OC(C)(C)C)=O)CC3COC4)N=2)=CC=1)=[C:53]=[O:54]>ClCCl.O1CCCC1.C(N(CC)CC)C>[CH3:55][NH:52][C:53](=[O:54])[NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:13]=[C:12]3[N:14]([CH2:17][C:18]([F:19])([F:21])[F:20])[N:15]=[CH:16][C:11]3=[C:10]([N:22]3[CH:27]4[CH2:28][N:29]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:30][CH:23]3[CH2:24][O:25][CH2:26]4)[N:9]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 6329MethylamineHCID 94429TriphosgeneHCID 66588941tert-butyl 9-(6-(4-aminophenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-3-oxa-7,9-diazabicyclo[3.3.1]nonane-7-carboxylateHCID 86629383HCID 86629383, compound

Product 1

HCID 57424695HCID 57424695, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

A solution of tert-butyl 9-(6-(4-aminophenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-3-oxa-7,9-diazabicyclo[3.3.1]nonane-7-carboxylate (230 mg, 0.45 mmol) in dichloromethane (6 mL) was treated triethylamine (520 μL), followed by triphosgene (90 mg, 0.30 mmol) as a solution in dichloromethane (2 mL). After the passage of 5 minutes, the appropriate nucleophile—in the case, 2.0 M methylamine solution in tetrahydrofuran (4 mL)—was added to tert-butyl 9-(6-(4-isocyanatophenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-3-oxa-7,9-diazabicyclo[3.3.1]nonane-7-carboxylate (“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 10% acetonitrile/90% of 0.1% aqueous trifluoroacetic acid to 100% acetonitrile to provide tert-butyl 9-(6-(4-(3-methylureido)phenyl)-1-(2,2,2-trifluoroethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-3-oxa-7,9-diazabicyclo[3.3.1]nonane-7-carboxylate. MS (ES+): 577.2 (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 10% acetonitrile/90% of 0.1% aqueous trifluoroacetic acid to 100% acetonitrile

Sources & evidence

ORD record
ord-adf274bdcd6c41f6b64de7a6dcf0549f
Source dataset
uspto-grants-2012_03
Patent number
US08129371B2

Reaction notes

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