Hydrochloric Acid → HCID 53325826, compound

HRID 216266Notes

Reaction equation

HRID 216266 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=2[Cl:20])[CH:3]=1.[NH:21]1[C:25]([CH:26]2[CH2:31][CH2:30][CH2:29][NH:28][CH2:27]2)=[N:24][N:23]=[N:22]1.C([O-])([O-])=O.[K+].[K+].Cl>CN1CCCC1=O.O>[Cl:20][C:14]1[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=1[CH2:12][CH2:11][NH:10][C:4]1[CH:3]=[C:2]([N:28]2[CH2:29][CH2:30][CH2:31][CH:26]([C:25]3[N:21]=[N:22][NH:23][N:24]=3)[CH2:27]2)[N:7]=[C:6]([O:8][CH3:9])[N:5]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 576360046-Chloro-N-[2-(2,4-dichlorophenyl)ethyl]-2-methoxy-4-pyrimidinamineHCID 178420779HCID 178420779, compound

Product 1

HCID 53325826HCID 53325826, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(2,4-dichloro-phenyl)-ethyl]-amine [300 mg, 0.9 mmol], 3-(1H-tetrazol-5-yl)-piperidine [383 mg, 2.25 mmol] and K2CO3 (373 mg, 2.7 mmol) in N-methylpyrollidinone (5 mL) is heated at 140° C. for 16 hours. The mixture is diluted with water (50 mL), acidified to pH 3 with 10% HCl and extracted three times with EtOAc (40 mL). The organic extracts from the acidic layer are combined and dried over magnesium sulfate, filtered and concentrated. The residue is subjected to chromatography on silica gel eluting with 15% ethyl methanol:DCM to afford an oil which is diluted with water (20 mL). A solid is formed and collected by filtration to afford [2-(2,4-dichloro-phenyl)-ethyl]-{2-methoxy-6-[3-(2H-tetrazol-5-yl)-piperidin-1-yl]-pyrimidin-4-yl}-amine [303 mg, 75%, Example 96] as a solid. LCMS: RT=1.95 minutes, MS: 449 (M+H). IC50=5 nM

Workup

  1. extractionextracted three times with EtOAc (40 mL)
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customDCM to afford an oil which
  6. customA solid is formed
  7. filtrationcollected by filtration

Sources & evidence

ORD record
ord-f92b134f78bb4d95ba13a15550a0073a
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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