Ethanol → ethyl 6-[[3-methyl-4-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]-5-nitrophenyl]carbamoylamino]hexanoate

HRID 723216Notes

Reaction equation

HRID 723216 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][NH:10][C:11]([NH:13][C:14]1[CH:19]=[C:18]([N+:20]([O-:22])=[O:21])[C:17](Br)=[C:16]([CH3:24])[CH:15]=1)=[O:12])[CH3:2].[C:26]([O:30][C:31](=[O:54])[NH:32][C:33]([C:35]1[S:36][C:37]([S:52][CH3:53])=[C:38]([S:40]([C:43]2[CH:48]=[CH:47][CH:46]=[C:45](B(O)O)[CH:44]=2)(=[O:42])=[O:41])[CH:39]=1)=[NH:34])([CH3:29])([CH3:28])[CH3:27].C([O-])([O-])=O.[Na+].[Na+].C(O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][NH:10][C:11]([NH:13][C:14]1[CH:15]=[C:16]([CH3:24])[C:17]([C:47]2[CH:46]=[CH:45][CH:44]=[C:43]([S:40]([C:38]3[CH:39]=[C:35]([C:33]([NH:32][C:31]([O:30][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:54])=[NH:34])[S:36][C:37]=3[S:52][CH3:53])(=[O:41])=[O:42])[CH:48]=2)=[C:18]([N+:20]([O-:22])=[O:21])[CH:19]=1)=[O:12])[CH3:2]

Participants

7

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 695868146-[3-(4-Bromo-3-methyl-5-nitro-phenyl)-ureido]-hexanoic acid ethyl esterHCID 140043492[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]boronic acid

Product 1

HCID 145857706ethyl 6-[[3-methyl-4-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]-5-nitrophenyl]carbamoylamino]hexanoateYield 37%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A 25 mL round bottom flask was charged with 6-[3-(4-bromo-3-methyl-5-nitro-phenyl)-ureido]-hexanoic acid ethyl ester (110 mg, 0.264 mmol, Example 278: step a), {[4-(3-dihydroxyboranyl-benzenesulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (234 mg, 0.529 mmol, Example 140: step a), aqueous Na2CO3 (2M, 1.06 mL, 2.12 mmol), ethanol (1.06 mL, anhydrous) and toluene (2.11 mL, anhydrous). A stir bar was added, the solution was degassed for 10 min, and Pd(PPh3)4 (76 mg, 65.8 μmol) was added. The reaction mixture was stirred under Ar at 80° C. for 5 hrs, then cooled to rt. The solvents were removed in vacuo. The residue was diluted in EtOAc, washed with brine, and dried over magnesium sulfate. Removal of solvents in vacuo followed by preparative TLC (50–100% EtOAc/hexanes) afforded the title compound as a brown oil (74 mg, 37%). ESI-MS (m/z): Calcd. for C33H41N5O9S3: 748.2 (M+1); found: 747.8.

Workup

  1. additionA stir bar was added
  2. customthe solution was degassed for 10 min
  3. temperaturecooled to rt
  4. customThe solvents were removed in vacuo
  5. additionThe residue was diluted in EtOAc
  6. washwashed with brine
  7. dry with materialdried over magnesium sulfate
  8. customRemoval of solvents in vacuo

Sources & evidence

ORD record
ord-925f772adbcb484c88ee797e724be638
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

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