Diisopropylethylamine → N-[1-(6-tert-butyl-2-methylpyridin-3-yl)ethyl]-2-(6,7-difluoro-1H-benzimidazol-1-yl)acetamide

HRID 1436345Notes

Reaction equation

HRID 1436345 reaction equation
CC1N=CC=CC=1C(N)=O.[C:11]([C:15]1[N:20]=[C:19]([CH3:21])[C:18]([CH:22]([NH2:24])[CH3:23])=[CH:17][CH:16]=1)([CH3:14])([CH3:13])[CH3:12].[F:25][C:26]1[CH:27]=[CH:28][C:29]2[N:33]=[CH:32][N:31]([CH2:34][C:35](O)=[O:36])[C:30]=2[C:38]=1[F:39].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>O>[C:11]([C:15]1[N:20]=[C:19]([CH3:21])[C:18]([CH:22]([NH:24][C:35](=[O:36])[CH2:34][N:31]2[C:30]3[C:38]([F:39])=[C:26]([F:25])[CH:27]=[CH:28][C:29]=3[N:33]=[CH:32]2)[CH3:23])=[CH:17][CH:16]=1)([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 122437052-MethylnicotinamideHCID 57939018HCID 57939018, compoundHCID 57939020[1-(6-Tert-butyl-2-methylpyridin-3-yl)ethyl]amine2×

Product 1

HCID 23633969N-[1-(6-tert-butyl-2-methylpyridin-3-yl)ethyl]-2-(6,7-difluoro-1H-benzimidazol-1-yl)acetamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

The title compound was synthesized according to the procedure described for the synthesis of 2-methylnicotinamide, starting from [1-(6-tert-butyl-2-methylpyridin-3-yl)ethyl]amine (intermediate 32) (31.5 mg, 0.16 mmol), 6,7-difluorobenzimidazole-1-acetic acid (35 mg 0.16 mmol) HATU (38 mg, 0.18 mmol) and DIPEA (71 μl, 0.41 mmol). Water was added and the reaction concentrated. The mixture was partitioned between ethyl acetate and water, and extracted 3 more times with ethyl acetate. The product was then purified by silica gel flash chromatography with acetone/hexanes (Yield 25 mg, 40%). 1H NMR (400 MHz, CD3OD-D4) d ppm 1.32 (s, 9 H), 1.47 (d, J=7.03 Hz, 3 H), 2.53-2.57 (m, 3 H), 5.04-5.15 (m, 2 H), 5.15-5.22 (m, 1 H), 7.16 (ddd, J=11.43, 8.79, 7.52 Hz, 1 H), 7.28 (d, J=8.20 Hz, 1 H), 7.41 (dd, J=8.89, 3.61 Hz, 1 H), 7.68 (d, J=8.20 Hz, 1 H), 8.11 (s, 1 H) MS [MH+] calc. 387.1996 found 387.3.

Workup

  1. concentrationthe reaction concentrated
  2. customThe mixture was partitioned between ethyl acetate and water
  3. extractionextracted 3 more times with ethyl acetate
  4. customThe product was then purified by silica gel flash chromatography with acetone/hexanes (Yield 25 mg, 40%)

Sources & evidence

ORD record
ord-2421f3a35cde4e84b4c0e86b148eca1e
Source dataset
uspto-grants-2009_11
Patent number
US07618993B2

Reaction notes

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