1,2-Dichloroethane → HCID 178474402, compound

HRID 518647Notes

Reaction equation

HRID 518647 reaction equation
[C:1]([N:4]=[C:5]=S)(=[O:3])[CH3:2].[NH2:7][C:8]1[C:9]([NH:23][C@@H:24]2[CH2:29][CH2:28][C@H:27]([C:30]([NH:32][CH:33]([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]2)=[CH:10][C:11]([O:14][CH2:15][CH2:16][N:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:12][CH:13]=1.NC(N)=S.C(Cl)CCl.CCN(C(C)C)C(C)C>O1CCOCC1.CO>[NH4+:4].[OH-:3].[C:1]([NH:4][C:5]1[N:23]([C@@H:24]2[CH2:25][CH2:26][C@H:27]([C:30]([NH:32][CH:33]([CH3:35])[CH3:34])=[O:31])[CH2:28][CH2:29]2)[C:9]2[CH:10]=[C:11]([O:14][CH2:15][CH2:16][N:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[N:12]=[CH:13][C:8]=2[N:7]=1)(=[O:3])[CH3:2]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 128851Acetyl isothiocyanateHCID 2723790ThioureaHCID 178457857HCID 178457857, compound

Product 2

HCID 14923Ammonium HydroxideHCID 178474402HCID 178474402, compoundYield 182.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

Acetyl isothiocyanate (1.755 mL, 19.97 mmol) was added to a heated (100° C. oil bath) solution of cis-4-(5-amino-2-(2-(piperidin-1-yl)ethoxy)pyridin-4-ylamino)-N-isopropylcyclohexanecarbox-amide (8.06 g, 19.97 mmol) in dioxane (100 mL). After 5 minutes, complete conversion to the thiourea intermediate was observed. The reaction was cooled to RT, and EDC (11.49 g, 59.9 mmol) and DIPEA (12.56 mL, 71.9 mmol) were added. Heating was resumed at 60° C. for 2.5 hours. The reaction mixture was pre-absorbed onto silica gel, and purified via silica gel chromatography, eluting with 90:10:1 DCM:MeOH:NH4OH to yield cis-4-(2-acetamido-6-(2-(piperidin-1-yl)ethoxy)-1H-imidazo[4,5-c]pyridin-1-yl)-N-isopropylcyclohexanecarboxamide (8.56 g, 18.19 mmol, 91% yield) as an orange solid. MS m/z=471.2 [M+H], calc 470.61 for C25H38N6O3.

Workup

  1. temperatureHeating
  2. waitwas resumed at 60° C. for 2.5 hours
  3. customThe reaction mixture was pre-absorbed onto silica gel
  4. custompurified via silica gel chromatography
  5. washeluting with 90:10:1 DCM

Sources & evidence

ORD record
ord-a19314f179964ca99d476f45781ee524
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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