1,1'-Carbonyldiimidazole → HCID 178484139, compound

HRID 1159394Notes

Reaction equation

HRID 1159394 reaction equation
C1N=CN([C:6]([N:8]2[CH:12]=N[CH:10]=[CH:9]2)=[O:7])C=1.[O:13]1[CH2:18][CH2:17][CH:16](C(O)=O)[CH2:15][CH2:14]1.[Cl:22][C:23]1[C:35]([CH2:36][N:37]2[CH2:41][CH2:40][CH2:39][CH2:38]2)=[CH:34][CH:33]=[CH:32][C:24]=1[O:25][C@H:26]1[CH2:29][C@H](CN)[CH2:27]1>C1COCC1>[ClH:22].[Cl:22][C:23]1[C:35]([CH2:36][N:37]2[CH2:41][CH2:40][CH2:39][CH2:38]2)=[CH:34][CH:33]=[CH:32][C:24]=1[O:25][C@H:26]1[CH2:29][C@H:10]([CH2:9][N:8]([CH3:12])[C:6]([CH:16]2[CH2:15][CH2:14][O:13][CH2:18][CH2:17]2)=[O:7])[CH2:27]1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 219302Oxane-4-carboxylic acidHCID 178511299HCID 178511299, compound

Product 1

HCID 178484139HCID 178484139, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

CDI (110 mg, 0.70 mmol) was added to a solution of tetrahydropyran-4-yl-carboxylic acid CAS 5337-03-1 (132 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 (162 mg, 53% yield). LC/MS data: 407.1 (M+H) (calculated for C22H31ClN2O3 406.96). 1H NMR-data (DMSO-d6): 10.31 (br. s, 1H, NH+); 7.73-8.12 (m, 1H, NH); 7.30-7.44 (m, 2H, Ar—H); 6.94-7.04 (m, 1H, Ar—H); 4.78-4.95 (m, 1H), 4.42-4.58 (m, 2H); 3.79-3.91 (m, 2H); 3.41-3.49 (m, 2H+ H2O); 3.25-3.34 (m, 2H); 3.09-3.24 (m, 4H); 2.24-2.45 (m, 4H); 1.98-2.19 (m, 4H); 1.83-1.94 (m, 2H); 1.83-1.94 (m, 4H).

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-61807c01629d405da5eb22650adfcbf7
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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