1,2-Dichloroethane → HCID 178457814, compound

HRID 518764Notes

Reaction equation

HRID 518764 reaction equation
[NH2:1][C:2]1[C:3]([NH:12][C@@H:13]2[CH2:18][CH2:17][C@H:16]([C:19]([NH:21][CH:22]([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)=[CH:4][C:5]([S:8]([CH3:11])(=[O:10])=[O:9])=[N:6][CH:7]=1.[F:25][C:26]1[CH:36]=[CH:35][C:29]([C:30]([N:32]=[C:33]=S)=[O:31])=[CH:28][CH:27]=1.CCN(C(C)C)C(C)C.C(Cl)CCl>C1COCC1.C(Cl)Cl>[F:25][C:26]1[CH:27]=[CH:28][C:29]([C:30](/[N:32]=[C:33]2/[N:12]([C@H:13]3[CH2:14][CH2:15][C@@H:16]([C:19](=[O:20])[NH:21][CH:22]([CH3:24])[CH3:23])[CH2:17][CH2:18]3)[C:3]3[CH:4]=[C:5]([S:8]([CH3:11])(=[O:9])=[O:10])[N:6]=[CH:7][C:2]=3[NH:1]/2)=[O:31])=[CH:35][CH:36]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 2490894-Fluorobenzoyl isothiocyanateHCID 178457868HCID 178457868, compound

Product 1

HCID 178457814HCID 178457814, compoundYield 47.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of cis-4-(5-Amino-2-(methylsulfonyl)pyridin-4-ylamino)-N-isopropylcyclohexanecarboxamide (0.069 g, 0.195 mmol) in THF (0.5 mL) was cooled to 0° C. and 4-fluorobenzoyl isothiocyanate (0.053 g, 0.292 mmol) was added as a THF solution. The mixture was stirred at 0° C. for 30 minutes and then was warmed to 20° C. and stirred for 1 hour. To the mixture was added DIPEA (0.051 mL, 0.292 mmol) and EDC (0.056 g, 0.292 mmol), and the reaction was heated at 60° C. for 1 hour. The reaction mixture was diluted with DCM and then washed with water and brine. The organic layer was concentrated under vacuum. The sample was purified by flash chromatography, eluting with 0-70% 90/10/1 DCM/MeOH/NH4OH:DCM to afford impure product as a light yellow solid. The impure material was further purified by preparative TLC, eluting with 90/10/1 DCM/MeOH/NH4OH:DCM to afford (E)-4-fluoro-N-(1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-6-(methylsulfonyl)-1H-imidazo[4,5-c]pyridin-2(3H)-ylidene)benzamide as a pale yellow solid (0.046 g, 47.1% yield). MS, m/z (C24H28FN5O4S); Calcd, 501.58. found 502.2 [M+H].

Workup

  1. temperaturewas warmed to 20° C.
  2. stirringstirred for 1 hour
  3. temperaturethe reaction was heated at 60° C. for 1 hour
  4. washwashed with water and brine
  5. concentrationThe organic layer was concentrated under vacuum
  6. customThe sample was purified by flash chromatography
  7. washeluting with 0-70% 90/10/1 DCM/MeOH/NH4OH
  8. customDCM to afford impure product as a light yellow solid
  9. customThe impure material was further purified by preparative TLC
  10. washeluting with 90/10/1 DCM/MeOH/NH4OH

Sources & evidence

ORD record
ord-213a1ac2c73a47f3a0fc27760c3cd9a6
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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