1,1'-Carbonyldiimidazole → HCID 178448263, compound

HRID 2199703Notes

Reaction equation

HRID 2199703 reaction equation
[Br:1][C:2]1[C:10]2[S:9][CH:8]=[C:7]([CH:11]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)[C@@H:12]([C:16]3[CH:24]=[CH:23][C:19]([C:20](O)=[O:21])=[CH:18][CH:17]=3)[CH2:13][CH2:14][CH3:15])[C:6]=2[CH:5]=[C:4]([CH3:32])[CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[NH2:45][C:46]1[NH:50][N:49]=[N:48][N:47]=1>CN(C=O)C.C(#N)C>[Br:1][C:2]1[C:10]2[S:9][CH:8]=[C:7]([CH:11]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)[C@@H:12]([C:16]3[CH:24]=[CH:23][C:19]([C:20]([NH:45][C:46]4[NH:50][N:49]=[N:48][N:47]=4)=[O:21])=[CH:18][CH:17]=3)[CH2:13][CH2:14][CH3:15])[C:6]=2[CH:5]=[C:4]([CH3:32])[CH:3]=1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 58513017HCID 58513017, compoundHCID 178509299HCID 178509299, compound

Product 1

HCID 178448263HCID 178448263, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-{(1S)-1-[(7-bromo-5-methyl-1-benzothien-3-yl)(4-chlorophenyl)methyl]butyl}benzoic acid (25.0 mg, 0.047 mmol) and CDI (26 mg, 0.16 mmol) in DMF (1.0 mL) was stirred at RT for 30 minutes in a sealed tube, then 5-amino-1H-tetrazole (23.0 mg, 0.260 mmol) was added. The mixture was heated at 100° C. for 12 hours, allowed to cool to RT, then diluted with acetonitrile. The mixture was purified by preparative reverse phase HPLC eluting with 47-100% acetonitrile/water+0.1% TFA. Following lyophilization, this afforded the title compound as a white solid. 1H NMR (500 MHz, d6-DMSO) δ 7.98 (br, 1H); 7.91 (d, J=8 Hz, 2H); 7.84 (br, 1H); 7.65 (d, J=8 Hz, 2H); 7.61 (d, J=8 Hz, 2H); 7.39 (d, J=8.5 Hz, 2H); 7.35 (br, 1H); 4.88 (d, J=12 Hz, 1H); 3.79 (t, J=11 Hz, 1H); 2.41 (s, 3H); 1.50-1.52 (m, 1H); 1.23-1.30 (m, 1H); 0.92 (q, J=7 Hz, 2H); 0.68 (t, J=7 Hz, 3H). LC2: 2.70 min. (M+H)+ 594.

Workup

  1. temperatureThe mixture was heated at 100° C. for 12 hours
  2. temperatureto cool to RT
  3. customThe mixture was purified by preparative reverse phase HPLC
  4. washeluting with 47-100% acetonitrile/water+0.1% TFA

Sources & evidence

ORD record
ord-3152c80d9f334fc486226974c5450de3
Source dataset
uspto-grants-2016_06
Patent number
US09359339B2

Reaction notes

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