1,1'-Carbonyldiimidazole → HCID 16222379, compound

HRID 639748Notes

Reaction equation

HRID 639748 reaction equation
[OH:1][N:2]=[C:3]([C:5]12[CH2:12][CH2:11][C:8]([C:13]3[N:17]([CH3:18])[C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[C:25]([F:28])([F:27])[F:26])=[N:15][N:14]=3)([CH2:9][CH2:10]1)[CH2:7][CH2:6]2)[NH2:4].[F:29][C:30]1([F:37])[CH2:33][CH:32]([C:34](O)=O)[CH2:31]1.C(N1C=CN=C1)(N1C=CN=C1)=O>C(Cl)Cl>[F:29][C:30]1([F:37])[CH2:33][CH:32]([C:34]2[O:1][N:2]=[C:3]([C:5]34[CH2:12][CH2:11][C:8]([C:13]5[N:17]([CH3:18])[C:16]([C:19]6[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=6[C:25]([F:28])([F:27])[F:26])=[N:15][N:14]=5)([CH2:9][CH2:10]3)[CH2:7][CH2:6]4)[N:4]=2)[CH2:31]1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 137777893,3-Difluorocyclobutane-1-carboxylic acidHCID 72262919N-hydroxy-4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]octane-1-carboximidamide

Product 1

HCID 16222379HCID 16222379, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N′-Hydroxy-4-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}bicyclo[2.2.2]octane-1-carboximidamide (1-G) (120 mg, 0.305 mmol) was added to a pre-stirred solution of 3,3-difluorocyclobutanecarboxylic acid 2-D (166 mg, 1.22 mmol) and carbonyldiimidazole (198 mg, 1.22 mmol) in CH2Cl2 (8 ml). The resulting mixture was stirred at room temperature for 48 h, then concentrated. The solid was resuspended in toluene and refluxed under nitrogen atmosphere for 3 h. The product was purified by C-18 reverse phase HPLC eluting with 30-80% acetonitrile/water with 0.1% TFA to yield 2-E as a white powder. MS (ESI+)=494.2 (M+1); 1H NMR (500 MHz, CDCl3): δ 2.09 (6H, m), 2.31 (6H, m), 3.03-3.11 (4H, m), 3.57-3.61 (4H, m), 7.56 (1H, m), 7.71 (2H, m), 7.86 (1H, m) ppm. Shh-Light II Assay: IC50: 1.4 μM.

Workup

  1. concentrationconcentrated
  2. temperaturerefluxed under nitrogen atmosphere for 3 h
  3. customThe product was purified by C-18 reverse phase HPLC
  4. washeluting with 30-80% acetonitrile/water with 0.1% TFA

Sources & evidence

ORD record
ord-5f1188499bc9499daeb916851c774116
Source dataset
uspto-grants-2010_04
Patent number
US07691887B2

Reaction notes

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