Triethylamine → HCID 11952412, compound

HRID 2243668Notes

Reaction equation

HRID 2243668 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)=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[CH2:12][NH:11][C:10]1=[O:40].[NH2:41][CH:42]1[CH2:47][CH2:46][N:45]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:44][CH2:43]1.C(N(CC)CC)C>C(Cl)Cl.CCOC(C)=O>[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:41][CH:42]3[CH2:43][CH2:44][N:45]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:46][CH2:47]3)[N:17]=[C:18]([C:19]3[CH:20]=[C:21]([C:22]([NH:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:23])[CH:32]=[CH:33][C:34]=3[CH3:35])[C:13]=2[CH2:12][NH:11][C:10]1=[O:40]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 12682914-Amino-1-Boc-piperidine2×HCID 11950098HCID 11950098, compound

Product 1

HCID 11952412HCID 11952412, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

The compound 3-[8-(2,6-difluorophenyl)-2-(methylsulfonyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-(phenylmethyl)benzamide (0.08 g, 0.14 mmol) was dissolved in CH2Cl2 (5 mL) and 1,1-dimethylethyl 4-amino-1-piperidinecarboxylate (0.0365 g, 0.175 mmol) and triethylamine (0.0284 g, 0.28 mmol) were added. The mixture was stirred under argon at room temperature overnight with only minor product formation. The reaction mixture was then heated to reflux for 24 h. The reaction still was not complete, so additional 1,1-dimethylethyl 4-amino-1-piperidinecarboxylate (0.146 g, 0.7 mmol) was added and the mixture stirred at reflux for 5 days. The solvents were pumped off in vacuo. The residue was taken up in EtOAc washed with 1M NaOH (2×), brine (1×), dried over anhydrous Na2SO4, filtered and evaporated The residue was flash chromatographed on silica gel (20 g) eluted with 0-50% EtOAc/CH2Cl2 to give the title compound as a white amorphous solid. mp (dec) 167-172° C.; LC-MS m/z 684 (M+H)+, 2.13 min (ret. time).

Workup

  1. temperatureThe reaction mixture was then heated
  2. temperatureto reflux for 24 h
  3. customThe reaction
  4. stirringthe mixture stirred
  5. temperatureat reflux for 5 days
  6. washwashed with 1M NaOH (2×), brine (1×)
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. customevaporated The residue
  10. customchromatographed on silica gel (20 g)
  11. washeluted with 0-50% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-ab56811c38ba41b087ac3fb4d20c2533
Source dataset
uspto-grants-2010_03
Patent number
US07674789B2

Reaction notes

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