1,1'-Carbonyldiimidazole → HCID 178431773, compound

HRID 1159393Notes

Reaction equation

HRID 1159393 reaction equation
C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:13][C:14]1([C:17]([OH:19])=O)[CH2:16][CH2:15]1.[Cl:20][C:21]1[C:33]([CH2:34][N:35]2[CH2:39][CH2:38][CH2:37][CH2:36]2)=[CH:32][CH:31]=[CH:30][C:22]=1[O:23][C@H:24]1[CH2:27][C@H:26]([CH2:28][NH2:29])[CH2:25]1>C1COCC1>[ClH:20].[Cl:20][C:21]1[C:33]([CH2:34][N:35]2[CH2:39][CH2:38][CH2:37][CH2:36]2)=[CH:32][CH:31]=[CH:30][C:22]=1[O:23][C@H:24]1[CH2:27][C@H:26]([CH2:28][NH:29][C:17]([C:14]2([CH3:13])[CH2:16][CH2:15]2)=[O:19])[CH2:25]1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 813261-Methylcyclopropanecarboxylic acidHCID 178511299HCID 178511299, compound

Product 1

HCID 178431773HCID 178431773, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

CDI (110 mg, 0.70 mmol) was added to a solution of 1-methylcyclopropanecarboxylic acid CAS 6914-76-7 (102 mg, 1.0 mmol) in THF (2 ml) at RT under stirring, the mixture was stirred at RT for 1 h. Example 386, ({trans-3-[2-Chloro-3-(pyrrolidin-1-ylmethyl)phenoxy]cyclobutyl}methyl) amine (200 mg, 0.7 mmol) was added to the mixture and the solution was stirred at RT for 20 h and evaporated. The residue was purified by chromatography (silica gel, 63-100 μm, 5 g, hexane/CHCl3 20:80→0:100, then CHCl3/MeOH 100:0→95:5). The residue was dissolved in ether (1 mL). 4N HCl/dioxane (0.20 mL) was added, and the reaction mixture was evaporated to dryness. The obtained crystals were washed with ether and dried in vacuo to give the title compound (135 mg, 48%) as beige crystals. LC/MS data: 377.1 (M+H) (calculated for C21H29ClN2O2 376.93). 1H NMR-data (DMSO-d6): 10.53 (br.s, 1H, NH+); 7.49-7.78 (m, 1H, NH); 7.32-7.43 (m, 2H, Ar—H); 6.95-7.03 (m, 1H, Ar—H); 4.80-4.92 (m, 1H), 4.42-4.56 (m, 2H); 3.39-3.47 (m, 2H); 3.18-3.25 (m, 2H); 3.07-3.18 (m, 2H); 2.39-2.47 (m, 1H); 2.27-2.34 (m, 2H); 1.97-2.17 (m, 4H); 1.84-1.95 (m, 2H); 1.25 (s, 3H); 0.92-0.96 (m, 2H), 0.46-0.52 (m, 2H).

Workup

  1. stirringthe mixture was stirred at RT for 1 h
  2. stirringthe solution was stirred at RT for 20 h
  3. customevaporated
  4. customThe residue was purified by chromatography (silica gel, 63-100 μm, 5 g, hexane/CHCl3 20:80→0:100
  5. dissolutionThe residue was dissolved in ether (1 mL)
  6. addition4N HCl/dioxane (0.20 mL) was added
  7. customthe reaction mixture was evaporated to dryness
  8. washThe obtained crystals were washed with ether
  9. customdried in vacuo

Sources & evidence

ORD record
ord-b57142f025c544d6be2f732b1d01c8ed
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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