Methanol → HCID 178501803, compound

HRID 2173945Notes

Reaction equation

HRID 2173945 reaction equation
[C:1]([C:3]1[CH:49]=[CH:48][C:6]2[N:7](COCC[Si](C)(C)C)[C:8]([C:10]([C:21]3[C:29]([O:30][CH3:31])=[CH:28][C:27]([CH3:32])=[C:26]4[C:22]=3[CH:23]=[CH:24][N:25]4C(OC(C)(C)C)=O)([O:15][CH2:16][C:17]([O:19][CH3:20])=[O:18])[C:11]([F:14])([F:13])[F:12])=[N:9][C:5]=2[CH:4]=1)#[N:2].C(C1C=CC2N=C(C(C3C(OC)=CC(C)=C4C=3C=CN4C(OC(C)(C)C)=O)(OCC(OC)=O)C(F)(F)F)N(COCC[Si](C)(C)C)C=2C=1)#N.CO>Cl>[C:1]([C:3]1[CH:49]=[CH:48][C:6]2[NH:7][C:8]([C:10]([C:21]3[C:29]([O:30][CH3:31])=[CH:28][C:27]([CH3:32])=[C:26]4[C:22]=3[CH:23]=[CH:24][NH:25]4)([O:15][CH2:16][C:17]([O:19][CH3:20])=[O:18])[C:11]([F:12])([F:13])[F:14])=[N:9][C:5]=2[CH:4]=1)#[N:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 86701506(+/-)-tert-butyl 4-(1-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-2,2,2-trifluoro-1-(2-methoxy-2-oxoethoxy)ethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylateHCID 86701507HCID 86701507, compound

Product 1

HCID 178501803HCID 178501803, compound

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (±)-tert-butyl 4-(1-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-2,2,2-trifluoro-1-(2-methoxy-2-oxoethoxy)ethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate and (±)-tert-butyl 4-(1-(6-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-2,2,2-trifluoro-1-(2-methoxy-2-oxoethoxy)ethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (510 mg, 0.711 mmol) was dissolved in 1.25 N HCl in MeOH (8.6 mL, 10.75 mmol), and stirred at 60° C. for 7 hours. The reaction mixture was then concentrated to dryness, dissolved in EtOAc, basified with a 15% aq. NH4OH solution at 0° C. and diluted with water. The organic layer was separated, dried over magnesium sulfate, filtered, concentrated and purified via FCC eluting with Heptane/EtOAc (0-60% of EtOAc) to provide the title compound. 1H NMR (400 MHz, Acetone) δ ppm 11.86 (br. s., 1H) 10.15 (br. s., 1H) 7.54-8.07 (m) 7.48 (d, J=8.08 Hz, 1H) 7.25 (t, J=2.91 Hz, 1H) 6.91-7.05 (m, 1H) 6.64 (s, 1H) 4.31 (m, 1H) 3.92-4.05 (m, 1H) 3.30-3.45 (s, 3H) 2.97-3.13 (s, 3H) 2.35-2.46 (s, 3H) HRMS calcd. for C23H19F3N4O4 (M+H)+ 473.1437. found 473.1438.

Workup

  1. concentrationThe reaction mixture was then concentrated to dryness
  2. dissolutiondissolved in EtOAc
  3. custombasified with a 15% aq. NH4OH solution at 0° C.
  4. additiondiluted with water
  5. customThe organic layer was separated
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified via FCC
  10. washeluting with Heptane/EtOAc (0-60% of EtOAc)

Sources & evidence

ORD record
ord-41c2cc54098e4ce1a058463828d14a7e
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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