6-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid pentafluorophenyl ester → (+/-)-cis-4-({[6-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carbonyl]-amino}-methyl)-3-fluoro-piperidine-1-carboxylic acid tert-butyl ester

HRID 2168804Notes

Reaction equation

HRID 2168804 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][NH2:15])[C@H:10]([F:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC1C([O:24][C:25]([C:27]2[N:28]=[N:29][C:30]([CH2:46][CH2:47][CH2:48][CH3:49])=[C:31]([C:33]3[CH:38]=[CH:37][C:36]([O:39][CH:40]4[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]4)=[CH:35][CH:34]=3)[CH:32]=2)=O)=C(F)C(F)=C(F)C=1F>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][NH:15][C:25]([C:27]2[N:28]=[N:29][C:30]([CH2:46][CH2:47][CH2:48][CH3:49])=[C:31]([C:33]3[CH:38]=[CH:37][C:36]([O:39][CH:40]4[CH2:41][CH2:42][CH2:43][CH2:44][CH2:45]4)=[CH:35][CH:34]=3)[CH:32]=2)=[O:24])[C@H:10]([F:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 866578236-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid pentafluorophenyl esterHCID 86657837tert-butyl (3S,4R)-4-(aminomethyl)-3-fluoropiperidine-1-carboxylate

Product 1

HCID 86657838(+/-)-cis-4-({[6-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carbonyl]-amino}-methyl)-3-fluoro-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (±)-cis-4-aminomethyl-3-fluoro-piperidine-1-carboxylic acid tert-butyl ester (0.65 mmol, 150 mg) in dichloromethane (3 mL) was added 6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid pentafluorophenyl ester (Example 93, 0.75 mmol, 400 mg) and TEA (1.3 mmol, 0.2 mL). After stirring the reaction at room temperature for 8 h, dichloromethane (5 mL) was added. The reaction was washed with saturated sodium bicarbonate solution (5 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated. Crude product was purified using hexane:ethyl acetate on 12 g normal phase ISCO flash column to provide (±)-cis-4-({[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carbonyl]-amino}-methyl)-3-fluoro-piperidine-1-carboxylic acid tert-butyl ester.

Workup

  1. customthe reaction at room temperature for 8 h
  2. washThe reaction was washed with saturated sodium bicarbonate solution (5 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customCrude product was purified

Sources & evidence

ORD record
ord-7a5f0d3591ff429e8522ff530f7a1b7b
Source dataset
uspto-grants-2015_06
Patent number
US09045461B2

Reaction notes

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