Diisopropylethylamine → 4-[2-(azetidin-1-ylcarbonyl)-3H-imidazo[4,5-b]pyridin-3-yl]-2-fluorobenzonitrile

HRID 2272711Notes

Reaction equation

HRID 2272711 reaction equation
Cl.[NH:2]1[CH2:5][CH2:4][CH2:3]1.C(N(CC)C(C)C)(C)C.[C:15]([C:17]1[CH:22]=[CH:21][C:20]([N:23]2[C:27]3=[N:28][CH:29]=[CH:30][CH:31]=[C:26]3[N:25]=[C:24]2[C:32](OCC)=[O:33])=[CH:19][C:18]=1[F:37])#[N:16].[Cl-].[Ca+2].[Cl-]>CO>[N:2]1([C:32]([C:24]2[N:23]([C:20]3[CH:21]=[CH:22][C:17]([C:15]#[N:16])=[C:18]([F:37])[CH:19]=3)[C:27]3=[N:28][CH:29]=[CH:30][CH:31]=[C:26]3[N:25]=2)=[O:33])[CH2:5][CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5284359Calcium ChlorideHCID 12308726Azetidine hydrochlorideHCID 86730071ethyl 3-(4-cyano-3-fluorophenyl)-3H-imidazo[4,5-b]pyridine-2-carboxylate

Product 1

HCID 783222944-[2-(azetidin-1-ylcarbonyl)-3H-imidazo[4,5-b]pyridin-3-yl]-2-fluorobenzonitrile

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of azetidine hydrochloride (120 mg, 1.3 mmol) and N,N-diisopropylethylamine (168 mg, 1.30 mmol) in methanol (2 mL) was stirred at room temperature for 1 hour. At this point, ethyl 3-(4-cyano-3-fluorophenyl)-3H-imidazo[4,5-b]pyridine-2-carboxylate (C16) (40 mg, 0.13 mmol) and calcium chloride (15 mg, 0.13 mmol) were added, and the reaction mixture was stirred at room temperature for an additional 2 hours. After removal of solvents in vacuo, the residue was purified by reversed phase HPLC (Column: DIKMA Diamonsil C18(2), 5 μm; Mobile phase A: 0.225% formic acid in water; Mobile phase B: 0.225% formic acid in acetonitrile; Gradient: 15% to 45% B) to provide the product as a yellow solid. Yield: 4.0 mg, 12 μmol, 9%. LCMS m/z 322.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.49 (dd, J=4.8, 1.3 Hz, 1H), 8.20 (dd, J=8.2, 1.4 Hz, 1H), 7.77-7.82 (m, 1H), 7.36-7.43 (m, 3H), 4.80-4.89 (m, 2H), 4.18-4.26 (m, 2H), 2.39-2.50 (m, 2H).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for an additional 2 hours
  2. customAfter removal of solvents in vacuo
  3. customthe residue was purified by reversed phase HPLC (Column: DIKMA Diamonsil C18(2), 5 μm; Mobile phase A: 0.225% formic acid in water; Mobile phase B: 0.225% formic acid in acetonitrile; Gradient: 15% to 45% B)

Sources & evidence

ORD record
ord-f0dfe2e804c74bdf92df2ac07027ee74
Source dataset
uspto-grants-2015_09
Patent number
US09120788B2

Reaction notes

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