N,N-Dimethylglycine → HCID 86686780, compound

HRID 1403145Notes

Reaction equation

HRID 1403145 reaction equation
[F:1][CH:2]([F:31])[C:3]1[N:7]([C:8]2[CH:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[C:10]([NH:20][CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[N:9]=2)[C:6]2[CH:27]=[CH:28][CH:29]=[CH:30][C:5]=2[N:4]=1.[CH3:32][N:33]([CH3:38])[CH2:34][C:35](O)=[O:36].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>O.CN(C)C=O>[F:31][CH:2]([F:1])[C:3]1[N:7]([C:8]2[CH:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[C:10]([NH:20][CH:21]3[CH2:26][CH2:25][N:24]([C:35](=[O:36])[CH2:34][N:33]([CH3:38])[CH3:32])[CH2:23][CH2:22]3)[N:9]=2)[C:6]2[CH:27]=[CH:28][CH:29]=[CH:30][C:5]=2[N:4]=1

Participants

7

Reactant 4

HCID 673N,N-DimethylglycineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86686778HCID 86686778, compound

Product 1

HCID 86686780HCID 86686780, compoundYield 41.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-morpholin-4-yl-N-piperidin-4-ylpyrimidin-2-amine (18 mg) and N,N-dimethylformamide (0.36 mL) were added N,N-dimethylglycine (4.8 mg), 1-hydroxybenzotriazole (6.2 mg), and N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (8.8 mg), and the mixture was stirred at room temperature for 6 hours. To the reaction mixture was added water, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and then the residue was purified by amino silica gel column chromatography (ethyl acetate, and subsequently chloroform:methanol=96:4). Desired fractions were combined and concentrated under reduced pressure. The residue was solidified by the addition of a small amount of diisopropyl ether to obtain 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-N-{1-[(dimethylamino)acetyl]piperidin-4-yl}-6-morpholin-4-ylpyrimidin-2-amine (9 mg) as a white powder.

Workup

  1. extractionfollowed by extraction with chloroform
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. customthe residue was purified by amino silica gel column chromatography (ethyl acetate, and subsequently chloroform
  5. concentrationconcentrated under reduced pressure
  6. additionThe residue was solidified by the addition of a small amount of diisopropyl ether

Sources & evidence

ORD record
ord-2448e6da41e8416a8be30eb3e718a848
Source dataset
uspto-grants-2014_12
Patent number
US08912180B2

Reaction notes

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