Hydrochloric Acid → HCID 178473444, compound

HRID 715603Notes

Reaction equation

HRID 715603 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[N:28]=[C:27]([O:29][C@@H:30]3[CH2:34][O:33][C@@H:32]4[C@H:35]([OH:38])[CH2:36][O:37][C@H:31]34)[N:26](COCC[Si](C)(C)C)[C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][CH:17]([NH:20][C:21](=[O:25])[O:22][CH2:23][CH3:24])[CH2:16][CH2:15]2)=[CH:10][CH:9]=1.OS([O-])(=O)=O.[K+].[OH-].[Na+].Cl>C(O)=O.O.O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[N:28]=[C:27]([O:29][C@@H:30]3[CH2:34][O:33][C@@H:32]4[C@H:35]([OH:38])[CH2:36][O:37][C@H:31]34)[NH:26][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][CH:17]([NH:20][C:21](=[O:25])[O:22][CH2:23][CH3:24])[CH2:16][CH2:15]2)=[CH:10][CH:9]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 516920Potassium bisulfateHCID 123408549HCID 123408549, compound

Product 1

HCID 178473444HCID 178473444, compound

Reagents, catalysts & solvents 3

HCID 284Formic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of ethyl 1-(4-(6-chloro-2-((3R,3aR,6R,6aR)-6-hydroxyhexahydrofuro[3,2-b]furan-3-yloxy)-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-b]pyridin-5-yl)phenyl)piperidin-4-ylcarbamate (44 mg) and KHSO4 (2 M aqueous solution, 40 μL) in formic acid (3 mL) is stirred for 3 hours at 60° C. After diluting with water and cooling to 0° C. NaOH (10 M aqueous solution) is added until the pH >11. Tetrahydrofurane (3 mL) is added and the mixture is stirred for 1 hour at room temperature. Hydrochloric acid (4 N) is added until pH=6. Then the mixture is partitioned between water and ethylacetate and the organic phase is washed with brine and dried (MgSO4). The solvents are evaporated in vacuo and the residue is purified by HPLC on reversed phase to give the title compound. LC (method 1): tR=0.81 min; Mass spectrum (ESI+): m/z=544 [M+H]+.

Workup

  1. temperaturecooling to 0° C
  2. stirringthe mixture is stirred for 1 hour at room temperature
  3. customThen the mixture is partitioned between water and ethylacetate
  4. washthe organic phase is washed with brine
  5. dry with materialdried (MgSO4)
  6. customThe solvents are evaporated in vacuo
  7. customthe residue is purified by HPLC on reversed phase

Sources & evidence

ORD record
ord-4a427c2ed30249d89a7c55457e4bb071
Source dataset
uspto-grants-2015_11
Patent number
US09187477B2

Reaction notes

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