Hydrochloric Acid → HCID 53251830, compound

HRID 473446Notes

Reaction equation

HRID 473446 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][N:13]=2)[N:8]=[C:7]([CH:15]([NH:17]C(=O)OC(C)(C)C)[CH3:16])[C:6]=1[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:4].Cl.O1CCOCC1.[NH2:38][C:39]1[C:44]([C:45]#[N:46])=[C:43](Cl)[N:42]=[CH:41][N:40]=1.CCN(C(C)C)C(C)C>C(OCC)C.CN(C=O)C.CCOC(C)=O>[NH2:38][C:39]1[N:40]=[CH:41][N:42]=[C:43]([NH:17][CH:15]([C:7]2[C:6]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)=[C:5]([C:3]([NH:2][CH3:1])=[O:4])[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][N:13]=3)[N:8]=2)[CH3:16])[C:44]=1[C:45]#[N:46]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 122782624-Amino-6-chloropyrimidine-5-carbonitrileHCID 58318616HCID 58318616, compound

Product 1

HCID 53251830HCID 53251830, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To tert-butyl 1-(4-(methylcarbamoyl)-3-phenyl-1,5-naphthyridin-2-yl)ethylcarbamate (110 mg, 0.27 mmol) was added 4N HCl in 1,4-dioxane (1 mL, 15 eq). The resulting mixture was stirred at rt for 30 min. The reaction mixture was diluted with ethyl ether (5 mL). The white solid was filtered and washed with ethyl ether and dried under vacuum. Mass Spectrum (ESI) m/e=307 (M+1). To a solution of the amine HCl salt in DMF (3 mL) was added 4-amino-6-chloropyrimidine-5-carbonitrile (41.8 mg, 1.0 eq) and DIEA (0.19 mL, 4.0 eq). The resulting mixture was heated to 105° C. for 2 h. After cool to rt, EtOAc (10 mL) was added and the mixture was washed with water (3×3 mL), brine and dried over sodium sulfate. The solvent was removed and the residue was purified by combiflash (1:20, MeOH/DCM) to afford 2-(1-(6-amino-5-cyanopyrimidin-4-ylamino)ethyl)-N-methyl-3-phenyl-1,5-naphthyridine-4-carboxamide. After chiral HPLC separation (isopropanol/hexane gradient, AD column), (S)-2-(1-(6-amino-5-cyanopyrimidin-4-ylamino)ethyl)-N-methyl-3-phenyl-1,5-naphthyridine-4-carboxamide and (R)-2-(1-(6-amino-5-cyanopyrimidin-4-ylamino)ethyl)-N-methyl-3-phenyl-1,5-naphthyridine-4-carboxamide were obtained as white solid.

Workup

  1. filtrationThe white solid was filtered
  2. washwashed with ethyl ether
  3. customdried under vacuum
  4. temperatureThe resulting mixture was heated to 105° C. for 2 h
  5. temperatureAfter cool to rt
  6. washthe mixture was washed with water (3×3 mL), brine
  7. dry with materialdried over sodium sulfate
  8. customThe solvent was removed
  9. customthe residue was purified by combiflash (1:20, MeOH/DCM)

Sources & evidence

ORD record
ord-905a41edf8ca4b1c921fec31b4fb3c94
Source dataset
uspto-grants-2014_01
Patent number
US08633313B2

Reaction notes

Loading…