1,1'-Carbonyldiimidazole → HCID 25007954, compound

HRID 573485Notes

Reaction equation

HRID 573485 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]1[N:12]([CH2:22][C:23](O)=[O:24])[C:13]2[C:18]([C:19](=[O:21])[CH:20]=1)=[CH:17][CH:16]=[CH:15][N:14]=2.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:38][C:39]([N:45]1[CH2:50][CH2:49][CH:48]([NH:51][CH2:52][C:53]2[CH:58]=[CH:57][C:56]([C:59]3[CH:64]=[CH:63][C:62]([C:65]([F:68])([F:67])[F:66])=[CH:61][CH:60]=3)=[CH:55][CH:54]=2)[CH2:47][CH2:46]1)([CH3:44])[C:40]([O:42][CH3:43])=[O:41]>CC(N(C)C)=O>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]1[N:12]([CH2:22][C:23]([N:51]([CH2:52][C:53]2[CH:58]=[CH:57][C:56]([C:59]3[CH:60]=[CH:61][C:62]([C:65]([F:67])([F:68])[F:66])=[CH:63][CH:64]=3)=[CH:55][CH:54]=2)[CH:48]2[CH2:49][CH2:50][N:45]([C:39]([CH3:38])([CH3:44])[C:40]([O:42][CH3:43])=[O:41])[CH2:46][CH2:47]2)=[O:24])[C:13]2[C:18]([C:19](=[O:21])[CH:20]=1)=[CH:17][CH:16]=[CH:15][N:14]=2

Participants

5

Reactant 3

HCID 682631,1'-Carbonyldiimidazole2×HCID 23614307HCID 23614307, compoundHCID 59264602HCID 59264602, compound

Product 1

HCID 25007954HCID 25007954, compoundYield 44.8%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of [2-[2-(2,3-difluorophenyl)ethyl]-4-oxo-1,8-naphthyridin-1(4H)-yl]acetic acid (Int. C2) (100 mg, 1 equiv), carbonyldiimidazole (50 mg, 1.05 equiv) and dimethylacetamide (4 ml) was stirred at 60° C. for 30 min then methyl 2-methyl-2-[4-({[4′-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]propanoate (Int. B1) (132 mg, 1.05 equiv) was added and the temperature raised to 80° C. for 2 h. A further portion of carbonyldiimidazole (0.5 equiv) was added and stirring continued at 80° C. for 15 h. After cooling the crude mixture was applied to reverse phase HPLC (Preparative Method A) to obtain methyl 2-[4-({[2-[2-(2,3-difluorophenyl)ethyl]-4-oxo-1,8-naphthyridin-1(4H)-yl]acetyl}{[4′-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]-2-methylpropanoate (99 mg).

Workup

  1. temperaturethe temperature raised to 80° C. for 2 h
  2. stirringstirring
  3. waitcontinued at 80° C. for 15 h

Sources & evidence

ORD record
ord-b5d1f2ab00344a36877bf47a4143a9c2
Source dataset
uspto-grants-2015_05
Patent number
US09029383B2

Reaction notes

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