1H-imidazol-2-ylmethanamine dihydrochloride → 3-{8-(2,6-difluorophenyl)-2-[(1H-imidazol-2-ylmethyl)amino]-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl}-4-methyl-N-(phenylmethyl)benzamide

HRID 223012Notes

Reaction equation

HRID 223012 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16](S(C)=O)[N:17]=[C:18]([C:19]3[CH:20]=[C:21]([CH:32]=[CH:33][C:34]=3[CH3:35])[C:22]([NH:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[O:23])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:39].Cl.Cl.[NH:42]1[CH:46]=[CH:45][N:44]=[C:43]1[CH2:47][NH2:48]>C(Cl)Cl.C(N(CC)CC)C.CCOC(C)=O.[OH-].[Na+]>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[C:14]2[N:15]=[C:16]([NH:48][CH2:47][C:43]3[NH:42][CH:46]=[CH:45][N:44]=3)[N:17]=[C:18]([C:19]3[CH:20]=[C:21]([CH:32]=[CH:33][C:34]=3[CH3:35])[C:22]([NH:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[O:23])[C:13]=2[CH:12]=[CH:11][C:10]1=[O:39]

Participants

7

Reactant 2

HCID 124178631H-imidazol-2-ylmethanamine dihydrochlorideHCID 592127113-[8-(2,6-difluorophenyl)-2-(methylsulfinyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methyl-N-(phenylmethyl)benzamide

Product 1

HCID 119481783-{8-(2,6-difluorophenyl)-2-[(1H-imidazol-2-ylmethyl)amino]-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl}-4-methyl-N-(phenylmethyl)benzamide

Reagents, catalysts & solvents 4

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

3-[8-(2,6-Difluorophenyl)-2-(methylsulfinyl)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methyl-N-(phenylmethyl)benzamide (0.084 g, 0.154 mmol) and (1H-imidazol-2-ylmethyl)amine dihydrochloride (0.039 g, 0.23 mmol) were dissolved in CH2Cl2 (5 mL) and triethylamine (0.7 mL). The resulting mixture was stirred under argon at room temperature overnight. The solvents were pumped off in vacuo, and the residue taken up in EtOAc and 1 N NaOH. The organic phase was washed with brine, dried over anhydrous Na2SO4 filtered and evaporated. The residue was flash chromatographed on silica gel (20 g) eluted with 6:1:0.05 CH2Cl2:isopropanol:NH4OH. The material isolated was not pure, and was rechromatographed on silica gel (20 g) eluted with 0-5% MeOH/CH2Cl2 to give the title compound as a white amorphous solid. mp (dec) 185-190° C. LC-MS m/z 578 (M+H)+, 1.76 min (ret time).

Workup

  1. washThe organic phase was washed with brine
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customchromatographed on silica gel (20 g)
  6. washeluted with 6:1:0.05 CH2Cl2
  7. customThe material isolated
  8. customwas rechromatographed on silica gel (20 g)
  9. washeluted with 0-5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-93e6ca4922104dfebd739930cff46c6e
Source dataset
uspto-grants-2012_06
Patent number
US08207176B2

Reaction notes

Loading…