Trimethyl borate → [3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]boronic acid

HRID 723110Notes

Reaction equation

HRID 723110 reaction equation
C([Mg]Cl)(C)C.[C:6]([O:10][C:11](=[O:32])[NH:12][C:13]([C:15]1[S:16][C:17]([S:30][CH3:31])=[C:18]([S:20]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25](Br)[CH:24]=2)(=[O:22])=[O:21])[CH:19]=1)=[NH:14])([CH3:9])([CH3:8])[CH3:7].[Li]CCCC.C[O:39][B:40](OC)[O:41]C>C1COCC1>[C:6]([O:10][C:11](=[O:32])[NH:12][C:13]([C:15]1[S:16][C:17]([S:30][CH3:31])=[C:18]([S:20]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([B:40]([OH:41])[OH:39])[CH:24]=2)(=[O:22])=[O:21])[CH:19]=1)=[NH:14])([CH3:9])([CH3:8])[CH3:7]

Participants

6

Reactant 4

HCID 8470Trimethyl borateHCID 145857672tert-butyl N-[4-(3-bromophenyl)sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamateHCID 178418339ButyllithiumHCID 178418918HCID 178418918, compound

Product 1

HCID 140043492[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]boronic acidYield 98.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 2M i-PrMgCl in THF (1.1 mL, 2.2 mmol) was added dropwise at 0° C. to {[4-(3-bromo-benzenesulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (0.5 g, 1.0 mmol) (Example 27c) in 5.0 mL THF. The solution was stirred for 20 mins at 0° C., then cooled to −78° C. and a solution of 2.5 M n-BuLi in hexanes (0.6 mL, 1.5 mmol) was added. The mixture was stirred for 5 mins then trimethylborate (0.35 mL, 3.3 mmol) was added at −78° C. and the mixture allowed to attain RT. The reaction was quenched with sat. NH4Cl (10 mL) and extracted with EtOAc (3×20 mL), dried over Na2SO4 and evaporated. The crude solid was purified by elution from a 5 g SPE with 10% MeOH/DCM to give 0.45 g (95%) of the title compound as a yellow solid: 1H NMR (400 MHz, CD3OD) δ 8.28 (m, 1H), 8.05 (m, 1H), 7.95 (m, 1H), 7.60 (m, 2H), 2.66 (s, 3H), 1.51 (s, 9H). Mass spectrum (ESI, m/z) calcd. for C17H21BN2O6S3 456.1, found 456.7 (M+H).

Workup

  1. temperaturecooled to −78° C.
  2. stirringThe mixture was stirred for 5 mins
  3. customto attain RT
  4. customThe reaction was quenched with sat. NH4Cl (10 mL)
  5. extractionextracted with EtOAc (3×20 mL)
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customThe crude solid was purified by elution from a 5 g SPE with 10% MeOH/DCM

Sources & evidence

ORD record
ord-d0d7d16c3e5f4f8e9303e58c50440e26
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

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