Sodium hydride → ethyl 3-[[3-methyl-2-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]phenyl]methoxy]propanoate

HRID 723137Notes

Reaction equation

HRID 723137 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:37])[NH:9][C:10]([C:12]1[S:13][C:14]([S:35][CH3:36])=[C:15]([S:17]([C:20]2[CH:21]=[C:22]([C:26]3[C:31]([CH3:32])=[CH:30][CH:29]=[CH:28][C:27]=3[CH2:33][OH:34])[CH:23]=[CH:24][CH:25]=2)(=[O:19])=[O:18])[CH:16]=1)=[NH:11])([CH3:6])([CH3:5])[CH3:4].Br[CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42]>CN(C=O)C>[CH2:44]([O:43][C:41](=[O:42])[CH2:40][CH2:39][O:34][CH2:33][C:27]1[CH:28]=[CH:29][CH:30]=[C:31]([CH3:32])[C:26]=1[C:22]1[CH:23]=[CH:24][CH:25]=[C:20]([S:17]([C:15]2[CH:16]=[C:12]([C:10]([NH:9][C:8]([O:7][C:3]([CH3:5])([CH3:6])[CH3:4])=[O:37])=[NH:11])[S:13][C:14]=2[S:35][CH3:36])(=[O:19])=[O:18])[CH:21]=1)[CH3:45]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 68320Ethyl 3-bromopropionateHCID 145857676tert-butyl N-[4-[3-[2-(hydroxymethyl)-6-methylphenyl]phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Product 1

HCID 145857715ethyl 3-[[3-methyl-2-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]phenyl]methoxy]propanoateYield 25.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a suspension of NaH (2.7 mg, 68 μmol, 60% oil dispersion) in DMF (0.1 mL) was added a solution of {[4-(2′-hydroxymethyl-6′-methyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (30 mg, 56.4 μmol) in DMF (0.1 mL), as prepared according to the procedure of step b of Example 213. The mixture was stirred at ambient temperature for 30 min, and then placed in an ice-water bath. After 20 min, a solution of ethyl 3-bromopropionate (8.6 μL, 67.0 μmol) in DMF (0.05 mL) was added once. Ice-water bath was removed, and the mixture was stirred for 16 h. H2O was added, and the mixture was extracted with EtOAc (3×). The extracts were combined, washed with H2O, dried over Na2SO4, concentrated, and flash chromatographed on silica gel, eluting with EtOAc/DCM (15%) followed by EtOAc/hexane (40%) to give the title compound (9 mg, 25%) yield) as an oil.

Workup

  1. customas prepared
  2. customplaced in an ice-water bath
  3. waitAfter 20 min
  4. customIce-water bath was removed
  5. stirringthe mixture was stirred for 16 h
  6. additionH2O was added
  7. extractionthe mixture was extracted with EtOAc (3×)
  8. washwashed with H2O
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customflash chromatographed on silica gel
  12. washeluting with EtOAc/DCM (15%)

Sources & evidence

ORD record
ord-067bc25cb55e495f9d42d6a0380c1c5f
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

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