Triethylamine → (-)-N-{1-[4-(1-Cyano-1-ethylpropyl)phenyl]ethyl}-2-(6,7-difluoro-1H-benzimidazol-1-yl)acetamide

HRID 603146Notes

Reaction equation

HRID 603146 reaction equation
[NH2:1][CH:2]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH2:15][CH3:16])([CH2:13][CH3:14])[C:11]#[N:12])=[CH:6][CH:5]=1)[CH3:3].[F:17][C:18]1[CH:19]=[CH:20][C:21]2[N:25]=[CH:24][N:23]([CH2:26][C:27](O)=[O:28])[C:22]=2[C:30]=1[F:31].CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH-].[Na+]>CC#N.O>[C:11]([C:10]([C:7]1[CH:8]=[CH:9][C:4]([CH:2]([NH:1][C:27](=[O:28])[CH2:26][N:23]2[C:22]3[C:30]([F:31])=[C:18]([F:17])[CH:19]=[CH:20][C:21]=3[N:25]=[CH:24]2)[CH3:3])=[CH:5][CH:6]=1)([CH2:13][CH3:14])[CH2:15][CH3:16])#[N:12]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 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 582984502-[4-(1-Aminoethyl)phenyl]-2-ethylbutanenitrile

Product 1

HCID 24850279(-)-N-{1-[4-(1-Cyano-1-ethylpropyl)phenyl]ethyl}-2-(6,7-difluoro-1H-benzimidazol-1-yl)acetamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Procedure

2-[4-(1-Aminoethyl)phenyl]-2-ethylbutanenitrile (520 mg, 2.41 mmol) prepared according to scheme 24, (6,7-difluoro-1H-benzimidazol-1-yl)acetic acid (510 mg, 2.41 mmol) prepared according to scheme 2 and Et3N (731 mg, 7.22 mmol, 1.00 mL) are mixed in MeCN (15.0 mL). HATU (915 mg, 2.41 mmol) is added and the mixture is stirred for 2 hours. 1N NaOH (40.0 mL) is added, and the aqueous phase is extracted with EtOAc (4 times 40.0 mL). The combined organic phases are dried with MgSO4, filtered and concentrated on the rotovaporator. The product is purified by HPLC: Gilson prep pumps, Flow rate: 30 ml/min, Column: Gemini (5%) 21.2×50 mm, Mobile phase: A=water (10 mM NH4CO3) B=MeCN, (804 mg, 1.96 mmol, 81%). 1H NMR (400 MHz, DMSO-D6) δ ppm 0.77 (t, J=7.32 Hz, 6H) 1.40 (d, J=7.03 Hz, 3H) 1.83-2.13 (m, 4H) 4.96 (ddd, J=14.65, 7.23, 7.03 Hz, 1H) 5.08 (s, 2H) 7.21 (ddd, J=11.57, 8.93, 7.62 Hz, 1H) 7.35-7.41 (m, 4H) 7.45 (ddd, J=8.84, 3.86, 0.78 Hz, 1H) 8.19-8.22 (m, 1H) 8.83 (d, J=8.01 Hz, 1H); MS [M+H], calcd: 411.0, found: 411.3.

Workup

  1. customprepared
  2. extractionthe aqueous phase is extracted with EtOAc (4 times 40.0 mL)
  3. dry with materialThe combined organic phases are dried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated on the rotovaporator
  6. customThe product is purified by HPLC

Sources & evidence

ORD record
ord-787a74a2196e465bb945c590869f2079
Source dataset
uspto-grants-2011_03
Patent number
US07906654B2

Reaction notes

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