Dimethylformamide → HCID 70929068, compound

HRID 1480003Notes

Reaction equation

HRID 1480003 reaction equation
[CH2:1]([C:8]1[N:13]=[N:12][C:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[N:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[C:23]([C:30]([OH:32])=O)=[CH:22][N:21]=3)[C@H:16]([CH3:33])[CH2:15]2)=[C:10]([CH3:34])[C:9]=1[CH3:35])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:36](Cl)(=[O:40])[C:37](Cl)=O.[CH3:42][N:43](C=O)C.CN>C1COCC1.CCOC(C)=O>[OH:40][CH2:36][CH2:37][N:43]([CH3:42])[C:30]([C:23]1[C:24]([C:26]([F:28])([F:29])[F:27])=[N:25][C:20]([N:17]2[CH2:18][CH2:19][N:14]([C:11]3[N:12]=[N:13][C:8]([CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[C:9]([CH3:35])[C:10]=3[CH3:34])[CH2:15][C@H:16]2[CH3:33])=[N:21][CH:22]=1)=[O:32]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 6329MethylamineHCID 65578Oxalyl chlorideHCID 67176532HCID 67176532, compound

Product 1

HCID 70929068HCID 70929068, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-[(R)-4-(6-benzyl-4,5-dimethyl-pyridazin-3-yl)-2-methyl-piperazin-1-yl]-4-trifluoromethyl-pyrimidine-5-carboxylic acid (45 mg, 0.1 mmol, 1 eq) in THF (2 mL) is added an excess of oxalyl chloride (100 μL, 1.2 mmol, 12 eq,) and a catalytic amount of DMF, and the resulting solution is stirred at rt for 45 min, at which time N-2-hydroxyethyl, N-methyl amine (200 μL, 2.5 mmol, 25 eq) is added, and the reaction is stirred for an additional 1 h. The reaction mixture is diluted with EtOAc (50 mL) and washed with water (2×10 mL) followed by brine (2×10 mL). The organic layer is dried over sodium sulfate and concentrated under reduced pressure to a white residue. The desired compound is isolated by silica gel chromatography (CH2Cl2—20% MeOH/CH2Cl2) as a white solid (43 mg, 79%).

Workup

  1. additionis added
  2. washwashed with water (2×10 mL)
  3. dry with materialThe organic layer is dried over sodium sulfate
  4. concentrationconcentrated under reduced pressure to a white residue

Sources & evidence

ORD record
ord-bfd8fd36467c4fbd916f915b8219f212
Source dataset
uspto-grants-2016_08
Patent number
US09409871B2

Reaction notes

Loading…