1,1'-Carbonyldiimidazole → HCID 178484144, compound

HRID 1159382Notes

Reaction equation

HRID 1159382 reaction equation
C1N=CN(C(N2C=NC=C2)=O)C=1.[O:13]1[CH2:18][CH2:17][CH:16]([C:19]([OH:21])=O)[CH2:15][CH2:14]1.[Cl:22][C:23]1[C:36]([CH2:37][N:38]2[CH2:42][CH2:41][CH2:40][CH2:39]2)=[C:35]([Cl:43])[CH:34]=[CH:33][C:24]=1[O:25][C@H:26]1[CH2:29][C@H:28]([CH2:30][NH:31][CH3:32])[CH2:27]1>C1COCC1>[ClH:22].[Cl:22][C:23]1[C:36]([CH2:37][N:38]2[CH2:42][CH2:41][CH2:40][CH2:39]2)=[C:35]([Cl:43])[CH:34]=[CH:33][C:24]=1[O:25][C@H:26]1[CH2:29][C@H:28]([CH2:30][N:31]([CH3:32])[C:19]([CH:16]2[CH2:15][CH2:14][O:13][CH2:18][CH2:17]2)=[O:21])[CH2:27]1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 219302Oxane-4-carboxylic acidHCID 178484142HCID 178484142, compound

Product 1

HCID 178484144HCID 178484144, compoundYield 171%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

CDI (227 mg, 1.40 mmol) was added to a solution of tetrahydropyran-4-yl-carboxylic acid (CAS 5337-03-1, 182 mg, 1.40 mmol) in THF (3 mL). The mixture was stirred for 30 min, and a solution of Example 377, ({trans-3-[2,4-Dichloro-3-(pyrrolidin-1-ylmethyl)phenoxy]cyclobutyl}methyl)methylamine (400 mg, 1.165 mmol) in THF (1 mL) was added. The reaction mixture was stirred for 16 h at room temperature and evaporated. CHCl3 (5 mL), a saturated solution of K2CO3 (0.5 mL), and water (0.5 mL) were added to the residue under stirring. The layers were separated, and the aqueous one was subjected to extraction with chloroform. The combined extracts were dried and evaporated. The residue was purified by chromatography (silica gel, 63-100 μm, 10 g, CHCl3/MeOH 100:0→80:10). Fractions containing the target product were evaporated. The residue was dissolved in ether (1 mL), and 4M HCl/dioxane (0.3 mL) was added under stirring. The obtained mixture was evaporated and dryed in vacuo to afford the title compound (490 mg, 85%) as a light-yellow amorphous solid. LCMS data: 455.1, 456.1, 457.1 (M+H) (calculated for C23H32Cl2N2O3 455.43). 1H NMR-data (DMSO-d6): 10.09 (brs, 1H, NH+), 7.55, 7.57 (2d, 1H, J=9 Hz, Ar—H); 7.12, 7.09 (2d, 1H, J=9 Hz, Ar—H); 4.88-5.09 (m, 1H); 4.60, 4.61 (2s, 2H, CH2); 3.74-3.90 (m, 2H), 3.23-3.58 (m, 8H); 2.80, 3.03 (2s, 3H, NCH3), 2.81-2.92 (m, 1H), 2.54-2.69 (m, 1H), 1.85-2.35 (m, 8H); 1.45-1.69 (m, 4H).

Workup

  1. stirringThe reaction mixture was stirred for 16 h at room temperature
  2. customevaporated
  3. additionCHCl3 (5 mL), a saturated solution of K2CO3 (0.5 mL), and water (0.5 mL) were added to the residue
  4. stirringunder stirring
  5. customThe layers were separated
  6. extractionthe aqueous one was subjected to extraction with chloroform
  7. customThe combined extracts were dried
  8. customevaporated
  9. customThe residue was purified by chromatography (silica gel, 63-100 μm, 10 g, CHCl3/MeOH 100:0→80:10)
  10. additionFractions containing the target product
  11. customwere evaporated
  12. dissolutionThe residue was dissolved in ether (1 mL)
  13. addition4M HCl/dioxane (0.3 mL) was added
  14. stirringunder stirring
  15. customThe obtained mixture was evaporated

Sources & evidence

ORD record
ord-f830e9d93f6f47fd818fb9a50dae2228
Source dataset
uspto-grants-2010_10
Patent number
US07812040B2

Reaction notes

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