Methylamine hydrochloride → HCID 178485301, compound

HRID 2174011Notes

Reaction equation

HRID 2174011 reaction equation
Cl.[CH3:2][NH2:3].[CH3:4][C:5]1[CH:6]=[C:7]2[C:16](=[O:17])[O:15][C:14]([C:22]3[NH:26][C:25]4[CH:27]=[CH:28][C:29]([C:31]#[N:32])=[CH:30][C:24]=4[N:23]=3)([C:18]([F:21])([F:20])[F:19])[C:8]2=[C:9]2[C:13]=1[NH:12][CH:11]=[CH:10]2>C1COCC1.C([Mg]Cl)(C)C>[C:31]([C:29]1[CH:28]=[CH:27][C:25]2[NH:26][C:22]([C:14]([C:8]3[C:7]([C:16]([NH:3][CH3:2])=[O:17])=[CH:6][C:5]([CH3:4])=[C:13]4[C:9]=3[CH:10]=[CH:11][NH:12]4)([OH:15])[C:18]([F:19])([F:21])[F:20])=[N:23][C:24]=2[CH:30]=1)#[N:32]

Participants

5

Reactant 2

HCID 6364545Methylamine hydrochlorideHCID 178421813HCID 178421813, compound

Product 1

HCID 178485301HCID 178485301, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 178418918HCID 178418918, compoundSolvent

Procedure

To a suspension of methylamine hydrochloride (102 mg, 1.51 mmol) in THF (0.5 mL), 2N isopropylmagnesium chloride in THF (1.51 mL, 3.03 mmol) was added. The reaction was stirred at room temperature for 3 hr, then a solution of (±)-2-(5-methyl-3-oxo-1-(trifluoromethyl)-3,6-dihydro-1H-furo[3,4-e]indol-1-yl)-1H-benzo[d]imidazole-5-carbonitrile (30 mg, 0.076 mmol) in THF (0.5 mL) was added. The reaction was allowed to stir at room temperature for 16 hours. The reaction mixture was quenched with 1N HCl aqueous solution and then neutralized by adding NaHCO3. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over Na2SO4. After concentration under reduced pressure, the residue was separated via silica gel flash column chromatography (CH2Cl2/EtOAc=0 to 100%) to give the title compound. 1H NMR (400 MHz, DMSO-d6, with about 3% METHANOL-d4) δ ppm 7.85 (d, J=2.0 Hz, 1H), 7.41-7.46 (m, 2H), 7.39 (d, J=0.8 Hz, 1H), 7.19 (dd, J=8.3, 1.8 Hz, 1H), 6.50 (d, J=2.5 Hz, 1H), 2.96 (s, 3H), 2.58 (s, 3H). HRMS calcd. for C21H16F3N5O2 (M+H)+ 428.1329. found 428.1333.

Workup

  1. additionwas added
  2. stirringto stir at room temperature for 16 hours
  3. customThe reaction mixture was quenched with 1N HCl aqueous solution
  4. additionby adding NaHCO3
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. concentrationAfter concentration under reduced pressure
  9. customthe residue was separated via silica gel flash column chromatography (CH2Cl2/EtOAc=0 to 100%)

Sources & evidence

ORD record
ord-6787c0afb4aa4c6583341cad1c171558
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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