1,1'-Carbonyldiimidazole → HCID 178446245, compound

HRID 2173811Notes

Reaction equation

HRID 2173811 reaction equation
[CH3:1][CH:2]([CH3:31])[CH2:3][CH:4]([C:22]1[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][N:23]=1)[NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.C(N(CC)C(C)C)(C)C.[NH:53]1[C:57]([CH2:58][NH2:59])=[N:56][N:55]=[N:54]1>CN(C)C=O.[Cl-].[NH4+]>[NH:53]1[C:57]([CH2:58][NH:59][C:26](=[O:28])[C:25]2[CH:29]=[CH:30][C:22]([CH:4]([NH:5][C:6]3[CH:7]=[CH:8][C:9]([C:12]4[CH:17]=[CH:16][C:15]([C:18]([F:20])([F:21])[F:19])=[CH:14][CH:13]=4)=[CH:10][CH:11]=3)[CH2:3][CH:2]([CH3:1])[CH3:31])=[N:23][CH:24]=2)=[N:56][N:55]=[N:54]1

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 67980686HCID 67980686, compoundHCID 178510704HCID 178510704, compound

Product 1

HCID 178446245HCID 178446245, compoundYield 13.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 6-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-ylamino) butyl)nicotinic acid (0.100 g, 0.233 mmol) in N,N-dimethylformamide (3.0 mL) was added 1,1′-carbonyldiimidazole (75.6 mg, 0.466 mmol) and N,N-diisopropylethylamine (181 mg, 1.40 mmol). The reaction was stirred for 30 minutes at 80° C. (1H-tetrazol-5-yl)methanamine (80.2 mg, 0.466 mmol) was added and the reaction continued to stir at 80° C. overnight. The reaction was diluted with saturated ammonium chloride and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by preparative HPLC (column: Boston Analytics Symmetrix ODS-H 150×30 mm, 5 μm; modifier: formic acid 0.225%; gradient: 10 to 80% MeCN in water) gave N-((1H-tetrazol-5-yl)methyl)-6-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-ylamino)butyl)nicotinamide (15.7 mg, 13%) as a light yellow solid. 1H NMR (400 MHz, CD3OD, δ): 9.35 (m, 1H), 8.98 (s, 1H), 8.15 (d, 1H), 7.72 (d, 4H), 7.50 (d, 1H), 7.35 (d, 2H), 6.64 (m, 3H), 4.75 (d, 2H), 4.55 (m, 1H), 1.75 (m, 2H), 1.55 (m, 1H), 0.95 (d, 3H), 0.85 (d, 3H). MS (M+1): 510.4.

Workup

  1. additionwas added
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by preparative HPLC (column: Boston Analytics Symmetrix ODS-H 150×30 mm, 5 μm; modifier: formic acid 0.225%; gradient: 10 to 80% MeCN in water)

Sources & evidence

ORD record
ord-d3ce3014ea984e8796afe11305fa5652
Source dataset
uspto-grants-2015_06
Patent number
US09056834B2

Reaction notes

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