Pivaloyl chloride → 2-(7-cyano-1H-benzimidazol-1-yl)-N-[4-(1-cyano-1-methylethyl)-2-methylbenzyl]acetamide

HRID 420002Notes

Reaction equation

HRID 420002 reaction equation
[C:1]([C:3]1[C:8]2[N:9]([CH2:12][C:13]([OH:15])=O)[CH:10]=[N:11][C:7]=2[CH:6]=[CH:5][CH:4]=1)#[N:2].CCN(C(C)C)C(C)C.C(Cl)(=O)C(C)(C)C.[NH2:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37]([C:40]([CH3:44])([CH3:43])[C:41]#[N:42])=[CH:36][C:35]=1[CH3:45]>C(Cl)Cl>[C:1]([C:3]1[C:8]2[N:9]([CH2:12][C:13]([NH:32][CH2:33][C:34]3[CH:39]=[CH:38][C:37]([C:40]([C:41]#[N:42])([CH3:43])[CH3:44])=[CH:36][C:35]=3[CH3:45])=[O:15])[CH:10]=[N:11][C:7]=2[CH:6]=[CH:5][CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 11195002(7-Cyano-1H-benzimidazol-1-yl)acetic acidHCID 582984482-[4-(Aminomethyl)-3-methylphenyl]-2-methylpropanenitrile

Product 1

HCID 598042592-(7-cyano-1H-benzimidazol-1-yl)-N-[4-(1-cyano-1-methylethyl)-2-methylbenzyl]acetamideYield 30.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(7-cyano-1H-benzimidazol-1-yl)acetic acid (86 mg, 0.43 mmol) prepared according to scheme 3 is dissolved in DCM (3 mL). DIPEA (0.1 mL) is added, followed by pivaloyl chloride (53 μL, 0.43 mmol). After 1 hour, 2-[4-(aminomethyl)-3-methylphenyl]-2-methylpropanenitrile (80 mg, 0.43 mmol) prepared according to scheme 19 is added. The mixture is stirred overnight at room temperature, concentrated under vacuo and purified on HPLCMS: Waters prep LCMS, 27 ml/min, X-Bridge Prep C18 OBD, 30×50 mm, 5 μm particle size, Mobile phase: A=water (10 mM NH4CO3) B=MeCN, Gradient used 30% to 50% B in A, in 10 min. The fractions are combined and freeze dried to give the desired product (47 mg, 0.13 mmol, 30%). MS (ESI) (M+1) 372.3. 1H NMR (400 MHz, DMSO-D6) δ ppm 1.65 (s, 6H) 2.31 (s, 3H) 4.29 (d, J=5.08 Hz, 2H) 5.26 (s, 2H) 7.25-7.29 (m, 1H) 7.30-7.40 (m, 3H) 7.73 (dd, J=7.62, 0.98 Hz, 1H) 8.03 (dd, J=8.20, 0.78 Hz, 1H) 8.38 (s, 1H) 8.74 (t, J=5.27 Hz, 1H).

Workup

  1. additionis added
  2. concentrationconcentrated under vacuo
  3. custompurified on HPLCMS
  4. waitin 10 min
  5. customfreeze dried

Sources & evidence

ORD record
ord-7768d85da6e1457d92c6ba11b14118c9
Source dataset
uspto-grants-2012_01
Patent number
US08093402B2

Reaction notes

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