Triethylamine → 2-(7-chloro-1H-benzimidazol-1-yl)-N-{1-[4-(1-cyano-1-methylethyl)-3-fluorophenyl]ethyl}acetamide

HRID 419992Notes

Reaction equation

HRID 419992 reaction equation
[Cl: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])=[C:21]([F:30])[CH:20]=1)[CH3:18].CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:1][C:2]1[C:7]2[N:8]([CH2:11][C:12]([NH:16][CH:17]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([C:26]#[N:27])([CH3:29])[CH3:28])=[C:21]([F:30])[CH:20]=3)[CH3:18])=[O:14])[CH:9]=[N:10][C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11206606(7-Chloro-1H-benzimidazol-1-yl)acetic acidHCID 666491832-[4-(1-Aminoethyl)-2-fluorophenyl]-2-methylpropanenitrile hydrochloride

Product 1

HCID 248501702-(7-chloro-1H-benzimidazol-1-yl)-N-{1-[4-(1-cyano-1-methylethyl)-3-fluorophenyl]ethyl}acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The amide is synthesized according to example 1 by mixing (7-chloro-1H-benzimidazol-1-yl)acetic acid (521 mg, 2.48 mmol) prepared according to scheme 1, 2-[4-(1-Aminoethyl)-2-fluorophenyl]-2-methylpropanenitrile hydrochloride 721 mg, 2.97 mmol) prepared according to scheme 7, Et3N (824 μL, 5.95 mmol) and HATU (1.13 g, 2.97 mmol) in DMF (10.0 mL). The product is purified by HPLC: Gilson prep pumps, Flow rate: 30 ml/min, Column: Gemini (5u) 21.2×50 mm, Mobile phase: A=water (0.075% TFA) B=MeCN (0.075% TFA), (421 mg as TFA salt, 0.82 mmol, 33%); 1H NMR (400 MHz, DMSO-D6) δ ppm 1.38 (d, J=7.03 Hz, 3H), 1.64-1.76 (m, 6H), 4.88-4.98 (m, 1H), 5.27 (s, 2H), 7.18-7.28 (m, 3H), 7.28-7.33 (m, 1 H), 7.41 (t, J=8.30 Hz, 1H), 7.65 (d, J=7.81 Hz, 1H), 8.47 (s, 1H), 8.85 (d, J=7.62 Hz, 1H). MS [M+H], calcd: 399.9. found: 399.3.

Workup

  1. customprepared
  2. customprepared
  3. customThe product is purified by HPLC

Sources & evidence

ORD record
ord-e38df4fabbb446b183c7bbf306fd651f
Source dataset
uspto-grants-2012_01
Patent number
US08093402B2

Reaction notes

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