Formaldehyde → Ammonia

HRID 402078Notes

Reaction equation

HRID 402078 reaction equation
Cl.Cl.[F:3][C@H:4]1[C@@H:9]([CH2:10][NH:11][C:12]([C:14]2[N:15]=[N:16][C:17]([CH2:33][CH2:34][CH2:35][CH3:36])=[C:18]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)=[CH:22][CH:21]=3)[CH:19]=2)=[O:13])[CH2:8][CH2:7][NH:6][CH2:5]1.C=O.[C:39](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[NH3:6].[F:3][C@H:4]1[C@@H:9]([CH2:10][NH:11][C:12]([C:14]2[N:15]=[N:16][C:17]([CH2:33][CH2:34][CH2:35][CH3:36])=[C:18]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)=[CH:22][CH:21]=3)[CH:19]=2)=[O:13])[CH2:8][CH2:7][N:6]([CH3:39])[CH2:5]1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 131730542(+/-)-cis-6-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid (3-fluoro-piperidin-4-ylmethyl)-amide dihydrochloride

Product 2

HCID 222AmmoniaHCID 58438382(+/-)-cis-6-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid (3-fluoro-1-methyl-piperidin-4-ylmethyl)-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (±)-cis-6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid (3-fluoro-piperidin-4-ylmethyl)-amide dihydrochloride (220 mg, 0.47 mmol) in dichloromethane (1 mL) was added formaldehyde (1 mL) and sodium triacetoxyborohydride (1 mmol, 210 mg). The reaction was stirred at room temperature for 3 h. Reaction was diluted with dichloromethane (5 mL) and washed with saturated sodium bicarbonate solution (5 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated. The crude product was purified using dichloromethane:2 M ammonia in methanol to give (±)-cis-6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazine-3-carboxylic acid (3-fluoro-1-methyl-piperidin-4-ylmethyl)-amide.

Workup

  1. customReaction
  2. washwashed with saturated sodium bicarbonate solution (5 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customThe crude product was purified

Sources & evidence

ORD record
ord-1718c7bd859b4776be0d981686609762
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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