Hydrochloric Acid → HCID 58843175, compound

HRID 1270993Notes

Reaction equation

HRID 1270993 reaction equation
ClC1C=CC(OC2C=CC(NC(=O)[NH:15][C@@H:16]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:17]([NH:19][CH2:20][CH2:21][N:22]([CH:26]([CH3:28])[CH3:27])[CH:23]([CH3:25])[CH3:24])=[O:18])=CC=2)=CC=1.Cl.O1CCOCC1.[F:46][C:47]1[CH:62]=[CH:61][C:50]([O:51][C:52]2[CH:57]=[CH:56][C:55]([N:58]=[C:59]=[S:60])=[CH:54][CH:53]=2)=[CH:49][CH:48]=1>C(Cl)Cl>[CH:26]([N:22]([CH:23]([CH3:25])[CH3:24])[CH2:21][CH2:20][NH:19][C:17](=[O:18])[C@@H:16]([NH:15][C:59]([NH:58][C:55]1[CH:54]=[CH:53][C:52]([O:51][C:50]2[CH:61]=[CH:62][C:47]([F:46])=[CH:48][CH:49]=2)=[CH:57][CH:56]=1)=[S:60])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)([CH3:27])[CH3:28]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 10459847HCID 10459847, compoundHCID 18450254HCID 18450254, compound2×

Product 1

HCID 58843175HCID 58843175, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of [(S)-1-(2-diisopropylamino-ethylcarbamoyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester (Example 3, step B) (0.093 g, 0.24 mmol) in CH2Cl2 (2 mL) a 4 M solution of HCl in dioxane (0.6 mL, 2.4 mmol) was added, and the mixture was stirred for 3 h at rt. The solvents were removed, and the residue was treated with CH2Cl2. The solvents were removed again under reduced pressure. The residue was dissolved in MeOH and treated with strongly basic ion exchange resin. After 10 min of stirring, the resin was filtered off and the solvents were removed. The residue was dissolved in CH2Cl2 (2 mL), and 4-(4-fluoro-phenoxy)-phenylisothiocyanate (0.064 g, 0.26 mmol) was added. After the mixture was stirred for 4 h, a small amount of 4-(4-fluoro-phenoxy)-phenylisothiocyanate (0.02 g) was added, and the mixture was stirred for 12 h. The crude mixture was purified by flash column chromatography using 0–20% MeOH(1% NH4OH)/CH2Cl2 afforded 0.07 g (55%) of the desired product. MS (electrospray): mass calculated for C30H37FN4O2S, 536.26; m/z found, 537.3 [M+H]+. 1H NMR (400 MHz, CD3OD): 7.26–6.89 (m, 13H), 5.17 (t, J=7 Hz, 1H), 3.17–2.96 (m, 6H), 2.44 (m, 2H), 1.02 (d, J=6.5 Hz, 12H).

Workup

  1. customThe solvents were removed
  2. additionthe residue was treated with CH2Cl2
  3. customThe solvents were removed again under reduced pressure
  4. dissolutionThe residue was dissolved in MeOH
  5. additiontreated with strongly basic ion exchange resin
  6. stirringAfter 10 min of stirring
  7. filtrationthe resin was filtered off
  8. customthe solvents were removed
  9. dissolutionThe residue was dissolved in CH2Cl2 (2 mL)
  10. stirringAfter the mixture was stirred for 4 h
  11. stirringthe mixture was stirred for 12 h
  12. customThe crude mixture was purified by flash column chromatography

Sources & evidence

ORD record
ord-d2c532c228774c2fab0f6d09fde2fe79
Source dataset
uspto-grants-2007_04
Patent number
US07202269B2

Reaction notes

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