Hydrochloric Acid → HCID 67419385, compound

HRID 1907808Notes

Reaction equation

HRID 1907808 reaction equation
[C:1]([C:5]1[N:6]=[CH:7][C:8]([C:11]([NH:13][C:14]2[CH:15]=[C:16]([C:21]3[CH:22]=[C:23]([NH:28][CH:29]4[CH2:34][CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30]4)[C:24](=[O:27])[NH:25][N:26]=3)[CH:17]=[CH:18][C:19]=2[F:20])=[O:12])=[N:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].Cl>CO.O1CCOCC1>[C:1]([C:5]1[N:6]=[CH:7][C:8]([C:11]([NH:13][C:14]2[CH:15]=[C:16]([C:21]3[CH:22]=[C:23]([NH:28][CH:29]4[CH2:34][CH2:33][CH2:32][NH:31][CH2:30]4)[C:24](=[O:27])[NH:25][N:26]=3)[CH:17]=[CH:18][C:19]=2[F:20])=[O:12])=[N:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86659961HCID 86659961, compound

Product 1

HCID 67419385HCID 67419385, compoundYield 65.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

In a 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer 10d (300 mg, 0.530 mmol) was dissolved in methanol (3.0 mL). To this solution 4M hydrogen chloride in dioxane (3 mL) was added, and this mixture was stirred at room temperature for 2 h under nitrogen. The reaction mixture was then concentrated under reduced pressure, and the resulting residue was partitioned between ethyl acetate (20 mL) and water (20 mL). The mixture was neutralized with saturated potassium carbonate to pH 6.5 (pH meter). The aqueous layer was separated and extracted with ethyl acetate (2×50 mL), The combined organic layers were washed with brine (100 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was evaporated under reduced pressure. The resulting residue was purified on a silica gel column eluting the desired product with 16% methanol in methylene chloride to afford a 65% yield (161 mg) of 10e as a off-white solid: mp 140-141° C.; 1H NMR (500 MHz, DMSO d6) δ 12.79 (s, 1H), 10.37 (s, 1H), 9.23 (s, 1H), 8.92 (s, 1H), 8.48 (d, 1H, J=7.5 Hz), 7.75 (m, 1H), 7.40 (m, 1H), 6.91 (s, 1H), 4.19 (d, 1H, J=9.5 Hz), 4.03 (d, 1H, J=13.0 Hz), 2.99-2.82 (m, 4H), 1.93 (m, 1H), 1.75 (m, 1H), 1.58 (m, 1H), 1.42 (s, 9H), 1.29 (m, 1H); MS (APCI−) m/z 464.6 (M−H).

Workup

  1. concentrationThe reaction mixture was then concentrated under reduced pressure
  2. customthe resulting residue was partitioned between ethyl acetate (20 mL) and water (20 mL)
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (2×50 mL)
  5. washThe combined organic layers were washed with brine (100 mL)
  6. dry with materialdried over sodium sulfate
  7. customThe drying agent was removed by filtration
  8. customthe filtrate was evaporated under reduced pressure
  9. customThe resulting residue was purified on a silica gel column
  10. washeluting the desired product with 16% methanol in methylene chloride

Sources & evidence

ORD record
ord-c66ecf5f221741da99dc1c44cc7e4acb
Source dataset
uspto-grants-2013_12
Patent number
US08598174B2

Reaction notes

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