Hydrochloric Acid → HCID 66855372, compound

HRID 2402450Notes

Reaction equation

HRID 2402450 reaction equation
[C:1]([C:3]1[C:4]([C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][C:33]=2[Cl:39])=[C:5]([C:20]2[N:21](C(OC(C)(C)C)=O)[CH2:22][CH2:23][N:24]=2)[S:6][C:7]=1[C:8]1[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]([CH:17]2[CH2:19][CH2:18]2)=[O:16])[CH:9]=1)#[N:2].O1CCOCC1.Cl>>[C:1]([C:3]1[C:4]([C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][C:33]=2[Cl:39])=[C:5]([C:20]2[NH:21][CH2:22][CH2:23][N:24]=2)[S:6][C:7]=1[C:8]1[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]([CH:17]2[CH2:19][CH2:18]2)=[O:16])[CH:9]=1)#[N:2]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-Dioxane2×HCID 66855533HCID 66855533, compound

Product 1

HCID 66855372HCID 66855372, compoundYield 76%

Procedure

To a solution of tert-butyl 2-[4-cyano-5-{2-[(cyclopropylcarbonyl)amino]pyridin-4-yl}-3-(2,4-dichlorophenyl)-2-thienyl]-4,5-dihydro-1H-imidazole-1-carboxylate (0.315 g, 0.541 mmol) in 1,4-Dioxane (4.00 mL, 51.2 mmol) was added 4.00 M of Hydrochloric acid in 1,4-Dioxane (1.35 mL, 5.41 mmol), stirred at room temperature overnight. Solvent was evaporated, residue was diluted with DCM (50 mL) and washed with 1M NaOH (5 mL). Layers were separated and the aqueous phase was extracted with DCM (3×50 mL). Combined organic extracts were dried with MgSO4, filtered and evaporated. The residue was purified using ISCO chromatography on silica gel, elution 5 to 80% ethyl acetate in hexanes to afford the product (0.197 g, 76%). LCMS: (FA) ES+, 482, 484. 1H NMR (400 MHz, d1-chloroform) δ: 8.66-8.64 (m, 1H) 8.41-8.38 (m, 1H), 8.25 (s, 1H), 7.61-7.59 (m, 1H), 7.48-7.45 (m, 1H), 7.44-7.41 (m, 1H), 7.37-7.34 (m, 1H), 3.97-3.68 (m, 2H), 3.60-3.25 (m, 2H), 1.57-1.52 (m, 1H), 1.17-1.11 (m, 2H), 0.95-0.88 (m, 2H).

Workup

  1. customSolvent was evaporated
  2. additionresidue was diluted with DCM (50 mL)
  3. washwashed with 1M NaOH (5 mL)
  4. customLayers were separated
  5. extractionthe aqueous phase was extracted with DCM (3×50 mL)
  6. dry with materialCombined organic extracts were dried with MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified
  10. washon silica gel, elution 5 to 80% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-b5f27159ed00424cb4888b58855acc69
Source dataset
uspto-grants-2014_08
Patent number
US08796314B2

Reaction notes

Loading…