Pivaloyl chloride → N-[4-(1-cyano-1-methylethyl)-2-methylbenzyl]-2-(6,7-difluoro-1H-benzimidazol-1-yl)acetamide

HRID 420001Notes

Reaction equation

HRID 420001 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].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:41]([C:40]([C:37]1[CH:38]=[CH:39][C:34]([CH2:33][NH:32][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)=[C:35]([CH3:45])[CH:36]=1)([CH3:44])[CH3:43])#[N:42]

Participants

6

Reactant 4

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 57939018HCID 57939018, compoundHCID 582984482-[4-(Aminomethyl)-3-methylphenyl]-2-methylpropanenitrile

Product 1

HCID 59804268N-[4-(1-cyano-1-methylethyl)-2-methylbenzyl]-2-(6,7-difluoro-1H-benzimidazol-1-yl)acetamideYield 35%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(6,7-difluoro-1H-benzimidazol-1-yl)acetic acid (91 mg, 0.43 mmol) prepared according to scheme 2 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, Column: 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 (59 mg, 0.15 mmol, 35%). MS (ESI) (M+1) 369.2. 1H NMR (400 MHz, DMSO-D6) δ ppm 1.67 (s, 6H) 4.33 (d, J=5.86 Hz, 2H) 5.10 (s, 2H) 7.23 (ddd, J=11.62, 8.89, 7.62 Hz, 1H) 7.32 (d, J=8.59 Hz, 2H) 7.44-7.51 (m, 3H) 8.21 (s, 1H) 8.80 (t, J=5.86 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-197ab24bbb0f42668dcdb86ab028a81b
Source dataset
uspto-grants-2012_01
Patent number
US08093402B2

Reaction notes

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