1,2-Dichloroethane → HCID 178496069, compound

HRID 518691Notes

Reaction equation

HRID 518691 reaction equation
[NH2:1][C:2]1[C:3]([NH:13][C@@H:14]2[CH2:19][CH2:18][C@H:17]([C:20]([NH:22][CH:23]([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)=[CH:4][C:5]([O:8][CH2:9][CH2:10][O:11][CH3:12])=[N:6][CH:7]=1.[F:26][C:27]1[CH:37]=[CH:36][C:30]([C:31]([N:33]=[C:34]=S)=[O:32])=[CH:29][CH:28]=1.CCN(C(C)C)C(C)C.C(Cl)CCl>C1COCC1>[F:26][C:27]1[CH:28]=[CH:29][C:30]([C:31](/[N:33]=[C:34]2/[N:13]([C@H:14]3[CH2:19][CH2:18][C@@H:17]([C:20](=[O:21])[NH:22][CH:23]([CH3:25])[CH3:24])[CH2:16][CH2:15]3)[C:3]3[CH:4]=[C:5]([O:8][CH2:9][CH2:10][O:11][CH3:12])[N:6]=[CH:7][C:2]=3[NH:1]/2)=[O:32])=[CH:36][CH:37]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 2490894-Fluorobenzoyl isothiocyanateHCID 178496144HCID 178496144, compound

Product 1

HCID 178496069HCID 178496069, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

To an ice-bath cooled solution of cis-4-(5-amino-2-(2-methoxyethoxy)pyridin-4-ylamino)-N-isopropylcyclohexanecarboxamide (156 mg, 0.445 mmol) in THF (0.8 mL) was added 4-fluorobenzoyl isothiocyanate (161 mg, 0.890 mmol) as a solution in THF (2 mL). The mixture was stirred 15 minutes, and then stirred another 30 minutes at RT. DIPEA (0.194 mL, 1.113 mmol) and EDC (213 mg, 1.113 mmol) were added, and the mixture was heated to 60° C. for 1 hour. The mixture was evaporated, and the residue was dissolved with 5% IPA/EtOAc (5 mL), washed with 1:1 aqueous NH4Cl (sat)/water, [1 mL total volume (×2)], brine, and the organic layer was dried over Na2SO4 and filtered. The mixture was purified via flash chromatography using a linear gradient of 0% to 5% of 1% NH4OH in MeOH in DCM. The title compound was collected as a white solid (110 mg, 50% yield). M/Z calc'd for C26H32FN5O4: 497.56. found 498 [M+H].

Workup

  1. stirringstirred another 30 minutes at RT
  2. customThe mixture was evaporated
  3. dissolutionthe residue was dissolved with 5% IPA/EtOAc (5 mL)
  4. washwashed with 1:1 aqueous NH4Cl (sat)/water, [1 mL total volume (×2)], brine
  5. dry with materialthe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. customThe mixture was purified via flash chromatography

Sources & evidence

ORD record
ord-2ff8d5becac44fe3b4d4cc15dd27db21
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

Loading…