Methylamine → HCID 178483018, compound

HRID 2173909Notes

Reaction equation

HRID 2173909 reaction equation
[C:1]([C:3]1[CH:42]=[CH:41][C:6]2[N:7](COCC[Si](C)(C)C)[C:8]([CH:10](O)[C:11]3[C:19]([O:20][CH:21]([F:23])[F:22])=[CH:18][C:17]([CH3:24])=[C:16]4[C:12]=3[CH:13]=[CH:14][N:15]4C(OC(C)(C)C)=O)=[N:9][C:5]=2[CH:4]=1)#[N:2].[C:43](C1C=CC2N=C(C(O)C3C(OC(F)F)=CC(C)=C4C=3C=CN4C(OC(C)(C)C)=O)N(COCC[Si](C)(C)C)C=2C=1)#[N:44].CN.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[F:23][CH:21]([F:22])[O:20][C:19]1[C:11]([CH:10]([NH:44][CH3:43])[C:8]2[NH:7][C:6]3[CH:41]=[CH:42][C:3]([C:1]#[N:2])=[CH:4][C:5]=3[N:9]=2)=[C:12]2[C:16](=[C:17]([CH3:24])[CH:18]=1)[NH:15][CH:14]=[CH:13]2

Participants

6

Reactant 4

HCID 6329MethylamineHCID 2724141Tetrabutylammonium FluorideHCID 86701444HCID 86701444, compoundHCID 86701445HCID 86701445, compound

Product 1

HCID 178483018HCID 178483018, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of a mixture of tert-butyl 4-((5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)(hydroxy)methyl)-5-(difluoromethoxy)-7-methyl-1H-indole-1-carboxylate and tert-butyl 4-((6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)(hydroxy)methyl)-5-(difluoromethoxy)-7-methyl-1H-indole-1-carboxylate (20 mg, 0.033 mmol) and methylamine (2.0M in THF, 0.17 mL, 0.33 mmol) in THF (0.33 mL) at room temperature, TBAF (1M in THF, 0.33 mL, 0.33 mmol) was added and the mixture was stirred at 55° C. After stirring overnight the reaction was cooled to room temperature, quenched with sat. aq. NH4Cl, extracted with EtOAc, and the organic extract was dried over MgSO4, filtered and concentrated. The resulting residue was purified by flash chromatography (0-100% EtOAc in heptanes) to provide the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.22 (br. s., 1H) 7.94 (br. s., 1H) 7.60 (d, J=8.34 Hz, 1H) 7.49 (dd, J=8.34, 1.52 Hz, 1H) 7.29 (t, J=2.78 Hz, 1H) 7.06 (t, J=75.5 Hz, 1H) 6.81 (s, 1H) 6.49 (dd, J=3.03, 2.02 Hz, 1H) 5.55 (s, 1H) 2.46 (d, J=0.76 Hz, 3H) 2.36 (s, 3H). HRMS calcd. for C20H17F2N5O (M+H)+ 382.1474. found 382.1489.

Workup

  1. stirringAfter stirring overnight the reaction
  2. temperaturewas cooled to room temperature
  3. customquenched with sat. aq. NH4Cl
  4. extractionextracted with EtOAc
  5. extractionthe organic extract
  6. dry with materialwas dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was purified by flash chromatography (0-100% EtOAc in heptanes)

Sources & evidence

ORD record
ord-37cb998d2b494a4097790bc912c49b44
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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