Diisopropylethylamine → HCID 178432444, compound

HRID 1875093Notes

Reaction equation

HRID 1875093 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]([Cl:20])=[C:8]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([Cl:19])[CH:18]=2)[C:14]#[N:15])[CH:9]=1.[Br:21][C:22]1[N:23]=[C:24]([CH3:30])[NH:25][C:26]=1[C:27](O)=[O:28].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>CCOCC.CN(C=O)C>[Br:21][C:22]1[N:23]=[C:24]([CH3:30])[NH:25][C:26]=1[C:27]([NH:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]([Cl:20])=[C:8]([O:10][C:11]2[CH:12]=[C:13]([C:14]#[N:15])[CH:16]=[C:17]([Cl:19])[CH:18]=2)[CH:9]=1)=[O:28]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 684872843-{[5-(Aminomethyl)-2-chlorophenyl]oxy}-5-chlorobenzonitrile hydrochlorideHCID 1784324484-bromo-2-methyl-1H-imidazole-5-carboxylic acid

Product 1

HCID 178432444HCID 178432444, compoundYield 274.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

DMF (5 mL) was added to a mixture of 3-{[5-(aminomethyl)-2-chlorophenyl]oxy}-5-chlorobenzonitrile hydrochloride (0.125 g, 0.379 mmol), 4-bromo-2-methyl-1H-imidazole-5-carboxylic acid (0.093 g, 0.455 mmol) and HATU (0.173 g, 0.455 mmol). The mixture was stirred for 5 min then DIPEA (0.132 ml, 0.758 mmol) was added and the yellow solution was stirred at RT under an atmosphere of nitrogen for 2 h. Saturated aqueous NaHCO3 solution (30 mL) and Et2O (10 mL) was added and the suspension was filtered to give 0.50 g of an insoluble white solid. The filtrate was extracted with ethyl acetate (75 mL) and washed with saturated aqueous Na HCO3 solution (2×50 mL), water (50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated. The crude material was purified on silica gel (hexanes/ethyl acetate) to give the title compound (0.075 g, 41%) in ca. 70% purity. The material was purified further by Reverse Phase HPLC (MeCN/H2O+0.1% TFA) to give the title compound (0.043 g, 24%) as a white powder. 1H NMR (400 MHz, DMSO-d6+CD3OD) δ ppm 7.66 (br. s., 1H), 7.54 (d, 1H), 7.16-7.35 (m, 4H), 4.44 (br. s., 2H), 2.25 (s, 3H). LCMS m/z 481.0 (M+H).

Workup

  1. stirringthe yellow solution was stirred at RT under an atmosphere of nitrogen for 2 h
  2. filtrationthe suspension was filtered

Sources & evidence

ORD record
ord-4e184a78fd684c0ab66510d04edbabc5
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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