Triethylamine → N-{1-[4-(1-cyano-1-methylethyl)-3-fluorophenyl]ethyl}-2-(6,7-difluoro-1H-benzimidazol-1-yl)acetamide

HRID 419991Notes

Reaction equation

HRID 419991 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[CH:8][N:7]([CH2:10][C:11]([OH:13])=O)[C:6]=2[C:14]=1[F:15].Cl.[NH2:17][CH:18]([C:20]1[CH:25]=[CH:24][C:23]([C:26]([CH3:30])([CH3:29])[C:27]#[N:28])=[C:22]([F:31])[CH:21]=1)[CH3:19].CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:27]([C:26]([C:23]1[CH:24]=[CH:25][C:20]([CH:18]([NH:17][C:11](=[O:13])[CH2:10][N:7]2[C:6]3[C:14]([F:15])=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[N:9]=[CH:8]2)[CH3:19])=[CH:21][C:22]=1[F:31])([CH3:29])[CH3:30])#[N:28]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57939018HCID 57939018, compoundHCID 666491832-[4-(1-Aminoethyl)-2-fluorophenyl]-2-methylpropanenitrile hydrochloride

Product 1

HCID 24850124N-{1-[4-(1-cyano-1-methylethyl)-3-fluorophenyl]ethyl}-2-(6,7-difluoro-1H-benzimidazol-1-yl)acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The amide is synthesized according to modified example 1 by mixing (6,7-difluoro-1H-benzimidazol-1-yl)acetic acid (781 mg, 3.68 mmol) prepared according to scheme 2, 2-[4-(1-Aminoethyl)-2-fluorophenyl]-2-methylpropanenitrile hydrochloride (1.07 mg, 4.41 mmol) prepared according to scheme 7, Et3N (1.23 mL, 8.82 mmol) and HATU (1.68 g, 4.41 mmol) in DMF (15.0 mL). The product is purified by HPLC: Gilson prep pumps, Flow rate: 30 ml/min, Column: Gemini (5u) 21.2×50 mm, Mobile phase: A=water (0.075% TFA) B=MeCN (0.075% TFA), (565 mg as TFA salt, 1.10 mmol, 30%); 1H NMR (400 MHz, DMSO-D6) δ ppm 1.38 (d, J=6.84 Hz, 3H), 1.71 (s, 6H), 4.87-5.00 (m, J=7.23, 7.23 Hz, 1H), 5.09 (s, 2H), 7.16-7.29 (m, 3H), 7.36-7.51 (m, 2H), 8.19 (s, 1H), 8.86 (d, J=7.62 Hz, 1H). MS [M+H], calcd: 401.4. found: 401.3.

Workup

  1. customprepared
  2. customprepared
  3. customThe product is purified by HPLC

Sources & evidence

ORD record
ord-0d1eb7784e514e998f570c23cde4dc84
Source dataset
uspto-grants-2012_01
Patent number
US08093402B2

Reaction notes

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