Triethylamine → 2-[(R)-4-(6-Chloro-4,5-dimethyl-pyridazin-3-yl)-2-methyl-piperazin-1-yl]-4-trifluoromethyl-pyrimidine-5-carboxylic acid methyl ester

HRID 1479991Notes

Reaction equation

HRID 1479991 reaction equation
C(N(CC)CC)C.[CH3:8][O:9][C:10]([C:12]1[C:13]([C:19]([F:22])([F:21])[F:20])=[N:14][C:15](Cl)=[N:16][CH:17]=1)=[O:11].[Cl:23][C:24]1[N:25]=[N:26][C:27]([N:32]2[CH2:37][CH2:36][NH:35][C@H:34]([CH3:38])[CH2:33]2)=[C:28]([CH3:31])[C:29]=1[CH3:30]>ClCCl>[CH3:8][O:9][C:10]([C:12]1[C:13]([C:19]([F:22])([F:21])[F:20])=[N:14][C:15]([N:35]2[CH2:36][CH2:37][N:32]([C:27]3[N:26]=[N:25][C:24]([Cl:23])=[C:29]([CH3:30])[C:28]=3[CH3:31])[CH2:33][C@H:34]2[CH3:38])=[N:16][CH:17]=1)=[O:11]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 3696469Methyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylateHCID 591915183-chloro-4,5-dimethyl-6-((R)-3-methyl-piperazin-1-yl)-pyridazine

Product 1

HCID 591914732-[(R)-4-(6-Chloro-4,5-dimethyl-pyridazin-3-yl)-2-methyl-piperazin-1-yl]-4-trifluoromethyl-pyrimidine-5-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Triethylamine (2.0 mL, 14.4 mmol, 2.9 eq) is added to a solution of 2-chloro-4-trifluoromethyl-pyrimidine-5-carboxylic acid methyl ester (1.25 g, 5.0 mmol, 1 eq), 3-chloro-4,5-dimethyl-6-((R)-3-methyl-piperazin-1-yl)-pyridazine (1.20 g, 5.0 mmol, 1 eq) in dichloromethane (40 mL) and the resulting solution is stirred at rt for 2 h. The reaction mixture is diluted with dichloromethane (50 mL) and washed with water (25 mL), then brine (25 mL). The organic layer is separated, dried over sodium sulfate and concentrated under reduced pressure to a white residue. The desired compound is isolated by silica gel chromatography (10-75% EtOAc/heptane) as a white solid (1.83 g, 82%).

Workup

  1. washwashed with water (25 mL)
  2. customThe organic layer is separated
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure to a white residue

Sources & evidence

ORD record
ord-be9c6bf0dfa24352b68de5fad9ab01d2
Source dataset
uspto-grants-2016_08
Patent number
US09409871B2

Reaction notes

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