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

HRID 1919843Notes

Reaction equation

HRID 1919843 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-diflurobenzimidazole-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-f56ece2a622146b2a6e2635ed160f995
Source dataset
uspto-grants-2012_05
Patent number
US08168668B2

Reaction notes

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