Hydrochloric Acid → 1-[4-(9-Phenyl-3-pyrimidin-2-yl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl)phenyl]cyclobutanamine hydrochloride

HRID 2064443Notes

Reaction equation

HRID 2064443 reaction equation
[C:1]1([C:7]2[C:8]([C:26]3[CH:31]=[CH:30][C:29]([C:32]4([NH:36]C(=O)OC(C)(C)C)[CH2:35][CH2:34][CH2:33]4)=[CH:28][CH:27]=3)=[N:9][C:10]3[CH:11]=[CH:12][N:13]4[C:19]([C:20]5[N:25]=[CH:24][CH:23]=[CH:22][N:21]=5)=[N:18][N:17]=[C:14]4[C:15]=3[CH:16]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[ClH:44].CCOC(C)=O>CO.C(Cl)Cl>[ClH:44].[C:1]1([C:7]2[C:8]([C:26]3[CH:27]=[CH:28][C:29]([C:32]4([NH2:36])[CH2:35][CH2:34][CH2:33]4)=[CH:30][CH:31]=3)=[N:9][C:10]3[CH:11]=[CH:12][N:13]4[C:19]([C:20]5[N:21]=[CH:22][CH:23]=[CH:24][N:25]=5)=[N:18][N:17]=[C:14]4[C:15]=3[CH:16]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 8857Ethyl Acetate2×HCID 57805499HCID 57805499, compound

Product 1

HCID 672538771-[4-(9-Phenyl-3-pyrimidin-2-yl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl)phenyl]cyclobutanamine hydrochloride

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl {1-[4-(9-phenyl-3-pyrimidin-2-yl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl)phenyl]cyclobutyl}carbamate (1-6d) (71 mg, 0.125 mmol) in MeOH (2 mL) and DCM (3 mL) was added a 4N solution of HCl in EtOAc (3 mL, 12 mmol). The sealed reaction mixture was permitted to stir at room temperature. After 4 hours the reaction mixture was concentrated. After 4 hours the reaction mixture was concentrated in vacuo. The resulting residue was purified by reverse phase column chromatography (Sunfire C18) eluting with 1 to 50% acetonitrile/(0.1% TFA/water) gradient. The appropriate fractions were concentrated in vacuo. The resulting residue was then dissolved in DCM (5 mL) & MeOH (5 mL), then added a 4N solution of HCl in EtOAc (5 mL, 20 mmol), then concentrated in vacuo to give 1-[4-(9-phenyl-3-pyrimidin-2-yl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl)phenyl]cyclobutanamine hydrochloride (1-10) as a tan solid. HRMS (M+H)+: observed=470.2098, calculated=470.2088.

Workup

  1. customThe sealed reaction mixture
  2. concentrationAfter 4 hours the reaction mixture was concentrated
  3. concentrationAfter 4 hours the reaction mixture was concentrated in vacuo
  4. customThe resulting residue was purified by reverse phase column chromatography (Sunfire C18)
  5. washeluting with 1 to 50% acetonitrile/(0.1% TFA/water) gradient
  6. concentrationThe appropriate fractions were concentrated in vacuo
  7. dissolutionThe resulting residue was then dissolved in DCM (5 mL)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8515b5cc95c2405c920e34d5c6b713db
Source dataset
uspto-grants-2012_10
Patent number
US08288407B2

Reaction notes

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