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 402076Notes

Reaction equation

HRID 402076 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-b538bf4d4b894f7da7dd9cf85425503f
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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