Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → N-{1-[4-(1-Cyano-1-methylethyl)phenyl]ethyl}-2-(7-fluoro-1H-benzimidazol-1-yl)acetamide

HRID 419981Notes

Reaction equation

HRID 419981 reaction equation
[F:1][C:2]1[C:7]2[N:8]([CH2:11][C:12]([OH:14])=O)[CH:9]=[N:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.Cl.[NH2:16][CH:17]([C:19]1[CH:24]=[CH:23][C:22]([C:25]([CH3:29])([CH3:28])[C:26]#[N:27])=[CH:21][CH:20]=1)[CH3:18].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C1C=CN=CC=1)C.CN(C=O)C>[C:26]([C:25]([C:22]1[CH:21]=[CH:20][C:19]([CH:17]([NH:16][C:12](=[O:14])[CH2:11][N:8]2[C:7]3[C:2]([F:1])=[CH:3][CH:4]=[CH:5][C:6]=3[N:10]=[CH:9]2)[CH3:18])=[CH:24][CH:23]=1)([CH3:29])[CH3:28])#[N:27]

Participants

6

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 112177812-(7-Fluoro-1H-1,3-benzodiazol-1-yl)acetic acidHCID 666490292-[4-(1-Aminoethyl)phenyl]-2-methylpropanenitrile hydrochloride

Product 1

HCID 24850277N-{1-[4-(1-Cyano-1-methylethyl)phenyl]ethyl}-2-(7-fluoro-1H-benzimidazol-1-yl)acetamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

N-{1-[4-(1-Cyano-1-methylethyl)phenyl]ethyl}-2-(7-fluoro-1H-benzimidazol-1-yl)acetamide is synthesized according to example 1 by mixing (7-fluoro-1H-benzimidazol-1-yl)acetic acid (200 mg, 1.03 mmol) prepared according to scheme 5, 2-[4-(1-aminoethyl)phenyl]-2-methylpropanenitrile hydrochloride (231 mg, 1.03 mmol) prepared according to scheme 6, DMAP (249 mg, 2.06 mmol) and HATU (391 mg, 1.03 mmol) in DMF (4.0 mL). The product is purified on HPLCMS: Waters prep LCMS, 27 ml/min, Column: SynerSi (4μ) Polar RP, 21.2×50 mm, Mobile phase: A=water (0.05% TFA) B=MeCN, Gradient used 30% to 50% B in A, in 10 min. The fractions are combined, NaOH 1 N is added and the desired compound is extracted with ethyl acetate. The combined organic fractions are concentrated under reduced pressure to yield the product (226 mg, 0.621 mmol, 60%). 1H NMR (400 MHz, METHANOL-D4) δ ppm 1.48 (d, J=7.03 Hz, 3H) 1.69 (s, 6H) 5.03 (q, J=6.90 Hz, 4H) 5.09 (d, J=16.99 Hz, 1 H) 5.14 (d, J=16.99 Hz, 1H) 7.00 (dd, J=11.43, 8.11 Hz, 1H) 7.20 (td, J=8.11, 4.88 Hz, 1H) 7.37 (d, J=8.20 Hz, 2H) 7.43-7.50 (m, 3H) 8.10 (s, 1H); MS [M+H], calcd: 365.2. found: 365.3.

Workup

  1. customprepared
  2. customprepared
  3. customThe product is purified on HPLCMS
  4. additionNaOH 1 N is added
  5. extractionthe desired compound is extracted with ethyl acetate
  6. concentrationThe combined organic fractions are concentrated under reduced pressure

Sources & evidence

ORD record
ord-f905888ee4194a04b28e6e3a8501e32c
Source dataset
uspto-grants-2012_01
Patent number
US08093402B2

Reaction notes

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