Diisopropylethylamine → HCID 178509914, compound

HRID 1875094Notes

Reaction equation

HRID 1875094 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]=[CH:24][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+]>C(OCC)(=O)C.CN(C=O)C>[Br:21][C:22]1[N:23]=[CH:24][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 1785249144-bromo-1H-imidazole-5-carboxylic acid

Product 1

HCID 178509914HCID 178509914, compoundYield 16%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

DMF (5 mL) was added to a mixture of 3-{[5-(aminomethyl)-2-chlorophenyl]oxy}-5-chlorobenzonitrile hydrochloride (0.115 g, 0.349 mmol), 4-bromo-1H-imidazole-5-carboxylic acid (0.070 g, 0.366 mmol) and HATU (0.159 g, 0.419 mmol). The mixture was stirred for 5 min then DIPEA (0.122 ml, 0.698 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 ethyl acetate (75 mL) were added. The organic layer was separated, washed with saturated aqueous NaHCO3 solution (2×50 mL), water (50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated. The crude material was purified by Reverse Phase HPLC (MeCN/water+0.1% TFA) to give the title compound (0.026 g, 16%) as a white solid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.74 (br. s., 1H), 7.49-7.56 (m, 2H), 7.30 (d, 1H), 7.16-7.24 (m, 3H), 4.57 (br. s., 2H). LCMS m/z 467.1 (M+H).

Workup

  1. stirringthe yellow solution was stirred at RT under an atmosphere of nitrogen for 2 h
  2. customThe organic layer was separated
  3. washwashed with saturated aqueous NaHCO3 solution (2×50 mL), water (50 mL), brine (50 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by Reverse Phase HPLC (MeCN/water+0.1% TFA)

Sources & evidence

ORD record
ord-922c618dc1f44ebb94933f52d5a3e54c
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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