1,1'-Carbonyldiimidazole → HCID 178484149, compound

HRID 1159386Notes

Reaction equation

HRID 1159386 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[CH:34]=[C:33]([CH2:35][N:36]2[CH2:40][CH2:39][CH2:38][CH2:37]2)[C:32]([Cl:41])=[CH:31][C:22]=1[O:23][C@H:24]1[CH2:27][C@H:26]([CH2:28][NH:29][CH3:30])[CH2:25]1>C1COCC1>[ClH:20].[Cl:20][C:21]1[CH:34]=[C:33]([CH2:35][N:36]2[CH2:40][CH2:39][CH2:38][CH2:37]2)[C:32]([Cl:41])=[CH:31][C:22]=1[O:23][C@H:24]1[CH2:25][C@H:26]([CH2:28][N:29]([CH3:30])[C:17]([C:14]2([CH3:13])[CH2:16][CH2:15]2)=[O:19])[CH2:27]1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 813261-Methylcyclopropanecarboxylic acidHCID 178484148HCID 178484148, compound

Product 1

HCID 178484149HCID 178484149, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

CDI (71 mg, 0.43 mmol) was added to a solution of 1-methylcyclopropanecarboxylic acid CAS 6914-76-7 (66 mg, 65 mmol) in THF (2 ml) at RT under stirring, the mixture was stirred at RT for 1 h. Example 381, ({trans-3-[2,5-dichloro-4-(pyrrolidin-1-ylmethyl)phenoxy]cyclobutyl}methyl)methylamine (150 mg, 0.43 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 (65 mg, 32%) as beige crystals. LC/MS data: 425.1 (M+H) (calculated for C22H30Cl2N2O2 425.4). 1H NMR-data (DMSO-d6): 10.77 (br.s, 1H, NH+); 8.01 (s, 1H, NH); 7.09 (s, 1H, Ar—H); 4.80-4.92 (m, 1H), 4.42-4.56 (m, 2H); 3.33-3.55 (m, 4H); 2.95-3.18 (m, 5H); 2.60-2.70 (m, 1H); 2.17-2.34 (m, 4H); 1.84-2.17 (m, 4H); 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-030316f5006c4394b7b27a808b6dede5
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

Loading…