HCID 178457845, compound → HCID 178457844, compound

HRID 518747Notes

Reaction equation

HRID 518747 reaction equation
[CH:1]([NH:4][C:5]([C@H:7]1[CH2:12][CH2:11][C@@H:10]([NH:13][C:14]2[C:19]([N+:20]([O-])=O)=[CH:18][N:17]=[C:16]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]>CCO.CCOC(C)=O.[Pd]>[NH2:20][C:19]1[C:14]([NH:13][C@@H:10]2[CH2:9][CH2:8][C@H:7]([C:5]([NH:4][CH:1]([CH3:3])[CH3:2])=[O:6])[CH2:12][CH2:11]2)=[CH:15][C:16]([N:23]2[CH2:24][CH2:25][O:26][CH2:27][CH2:28]2)=[N:17][CH:18]=1

Participants

5

Reactant 1

HCID 178457845HCID 178457845, compound

Product 1

HCID 178457844HCID 178457844, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of cis-N-isopropyl-4-(2-morpholino-5-nitropyridin-4-ylamino)cyclohexanecarboxamide (121 mg, 0.309 mmol) in EtOH (5 mL) and EtOAc (3 mL) was added 10% palladium on carbon (32.9 mg, 0.031 mmol). The reaction was stirred under a hydrogen atmosphere (H2 balloon) at RT. After 3 hours, the reaction mixture was filtered through Celite® brand filter aid (washed with MeOH and DCM), and concentrated to afford cis-4-(5-amino-2-morpholinopyridin-4-ylamino)-N-isopropylcyclohexane-carboxamide as a dark oil. The diamine was dissolved in THF (3 mL), and 4-fluorobenzoyl isothiocyanate (61.8 mg, 0.341 mmol) was added. The reaction was stirred at 0° C. for 15 minutes, and then EDC (89 mg, 0.465 mmol) and DIPEA (0.081 mL, 0.465 mmol) were added. The reaction was stirred at 60° C. for 2 hours and then overnight at RT. After 16 hours, the reaction mixture was concentrated, and adsorbed onto a plug of silica gel. The residue was purified by column chromatography, eluting with 0-100% EtOAc in DCM, to provide (E)-4-fluoro-N-(1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-6-morpholino-1H-imidazo[4,5-c]pyridin-2(3H)-ylidene)benzamide as a light-yellow powder (38 mg, 24.11% yield). MS, m/z (C27H33FN6O3): calcd, 508.3. found, 509.1 [M+H].

Workup

  1. filtrationthe reaction mixture was filtered through Celite® brand
  2. filtrationfilter
  3. washaid (washed with MeOH and DCM)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-cf42f96f02ef4982b5a1319fdfa2a5df
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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