Methanol → HCID 178500072, compound

HRID 2174108Notes

Reaction equation

HRID 2174108 reaction equation
[C:1]([C:3]1[CH:44]=[CH:43][C:6]2[N:7](COCC[Si](C)(C)C)[C:8]([CH:10]([C:16]3[C:24]([O:25][CH3:26])=[CH:23][C:22]([CH3:27])=[C:21]4[C:17]=3[CH:18]=[CH:19][N:20]4C(OC(C)(C)C)=O)[CH2:11][C:12]([O:14][CH3:15])=[O:13])=[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)CC(OC)=O)N(COCC[Si](C)(C)C)C=2C=1)#N.CO.[OH-].[NH4+]>Cl>[C:1]([C:3]1[CH:44]=[CH:43][C:6]2[NH:7][C:8]([CH:10]([C:16]3[C:24]([O:25][CH3:26])=[CH:23][C:22]([CH3:27])=[C:21]4[C:17]=3[CH:18]=[CH:19][NH:20]4)[CH2:11][C:12]([O:14][CH3:15])=[O:13])=[N:9][C:5]=2[CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 14923Ammonium HydroxideHCID 86701748HCID 86701748, compoundHCID 86701749HCID 86701749, compound

Product 1

HCID 178500072HCID 178500072, compound

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of (±)-tert-butyl 4-(1-(5-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-2-yl)-3-methoxy-3-oxopropyl)-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)-3-methoxy-3-oxopropyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 145-B) (400 mg, 0.646 mmol) was dissolved in 1.25M HCl in MeOH (20 mL, 25.00 mmol) and heated at 65° C. for 22 hrs. The reaction mixture was cooled down to 0° C. and neutralized with ammonium hydroxide. The layers were separated and the aqueous layer was extracted with AcOEt/heptanes (4:1) (3 x). The combined organic layers were dried over MgSO4, filtered and concentrated to give crude product that was purified via FCC with Heptane/AcOEt (100/0 to 0/100) to obtain the title compound. MS (ESI+) m/z 389.36 (M+H).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with AcOEt/heptanes (4:1) (3 x)
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give crude product that
  7. customwas purified via FCC with Heptane/AcOEt (100/0 to 0/100)

Sources & evidence

ORD record
ord-61092213f9474720868b1da04bd3eafc
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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