Triethylamine → HCID 59804267, compound

HRID 420000Notes

Reaction equation

HRID 420000 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].C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.[NH2:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]([CH3:42])([CH3:41])[C:39]#[N:40])=[CH:34][CH:33]=1>C(Cl)Cl>[C:39]([C:38]([C:35]1[CH:34]=[CH:33][C:32]([CH2:31][NH:30][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)=[CH:37][CH:36]=1)([CH3:42])[CH3:41])#[N:40]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 57939018HCID 57939018, compoundHCID 582984752-[4-(Aminomethyl)phenyl]-2-methylpropanenitrile

Product 1

HCID 59804267HCID 59804267, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(6,7-difluoro-1H-benzimidazol-1-yl)acetic acid (42 mg, 0.2 mmol) prepared according to scheme 2 is dissolved in CH2Cl2 (2 mL). Triethylamine (83 μL, 0.6 mmol) is added, followed by pivaloyl chloride (25 μL, 0.2 mmol). After 30 minutes, 2-[4-(aminomethyl)phenyl]-2-methylpropanenitrile (35 mg, 0.2 mmol) prepared according to scheme 18 is added dissolved in 1 mL of CH2Cl2. 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 40% to 60% B in A, in 10 min. The fractions are combined and freeze dried to give the desired product (17 mg, 0.05 mmol, 25%). MS (ESI) (M+1) 383.3. 1H NMR (400 MHz, DMSO-D6) δ ppm 1.65 (s, 6H) 2.30 (s, 3H) 4.29 (d, J=5.47 Hz, 2H) 5.09 (s, 2H) 7.19-7.31 (m, 3H) 7.32-7.35 (m, 1H) 7.47 (dd, J=8.98, 3.91 Hz, 1H) 8.22 (s, 1H) 8.66-8.74 (m, 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-7e2efb95b5724504886a199ed3796403
Source dataset
uspto-grants-2012_01
Patent number
US08093402B2

Reaction notes

Loading…