Sodium Carbonate → HCID 145857704, compound

HRID 723194Notes

Reaction equation

[C:1]([O:5][C:6](=[O:27])[NH:7][C:8]([C:10]1[S:11][C:12]([S:25][CH3:26])=[C:13]([S:15]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20](Br)[CH:19]=2)(=[O:17])=[O:16])[CH:14]=1)=[NH:9])([CH3:4])([CH3:3])[CH3:2].[C:28]([O-:31])([O-])=[O:29].[Na+].[Na+].[C:34]1([CH3:40])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[CH3:41]CO>>[CH3:41][O:31][C:28]([C:36]1[CH:37]=[CH:38][C:39]([C:20]2[CH:21]=[CH:22][CH:23]=[C:18]([S:15]([C:13]3[CH:14]=[C:10]([C:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:27])=[NH:9])[S:11][C:12]=3[S:25][CH3:26])(=[O:17])=[O:16])[CH:19]=2)=[C:34]([CH3:40])[CH:35]=1)=[O:29]

Participants

Reactant 3

HCID 10340Sodium Carbonate

HCID 21863594Toluene ethanol

HCID 145857672tert-butyl N-[4-(3-bromophenyl)sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Product 1

HCID 145857704HCID 145857704, compound

Procedure

Following the same procedure as in Example 220, step a, reaction of 4-bromo-3-methyl-benzoic acid methyl ester (1.75 gm, 7.6 mmol), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.3 mL, 23 mmol, Aldrich Chemical Company), PdCl2(PPh3)2 (530 mg, 0.76 mmol, Strem Chemicals Inc, Newburyport, Mass.), Et3N (6.3 mL, 46 mmol), and dioxane (30 mL) afforded 1.2 gm of a clear oil (79%) after purification (SiO2, flash elution: 30% EtOAc in hexanes. The above boronate ester (220 mg, 0.8 mmol) was reacted according to the procedure used in Example 1, step c, with {[4-(3-bromo-benzenesulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (100 mg, 0.8 mmol, as prepared in Example 27, step c), tetrakis(triphenylphosine)palladium(0) (58 mg, 0.05 mmol, Strem Chemicals Inc, Newburyport, Mass.), Na2CO3 (1.6 mL, 2 M), and toluene/EtOH mixture (2:1, 2.4 mL) to afford 3′-[5-(tert-butoxycarbonylamino-imino-methyl)-2-methylsulfanyl-thiophene-3-sulfonyl]-2-methyl-biphenyl-4-carboxylic acid methyl ester after purification (preparative TLC, 1:3 EtOAc/hexanes, 2000μ SiO2 plate). ESI-MS (m/z): Calcd. for C26H28N2O6S3: 560.7; found: 461.1 (M−Boc). The above methyl benzoate (45 mg. 0.08 mmol) was treated with 1 N NaOH in MeOH (1:1) and stirred at 50° C. overnight. The reaction mixture was neutralized with acetic acid, the solvents were removed in vacuo, and the residue was subjected to TFA treatment followed by C18-HPLC purification as described in Example 220, step c to afford the title compound as a white solid. 1H-NMR (CD3OD; 400 MHz) δ 8.35 (s, 1H), 8.06–8.11 (m, 1H), 8.00–8.03 (m, 2H), 7.95 (m, 1H), 7.72–7.76 (m, 2H), 7.35 (d, 1H, J=7.9 Hz), 2.75 (s, 3H), 2.30 (s, 3H). ESI-MS (m/z): Calcd. for C20H18N2O4S3: 447.1 (M+H); found: 447.1.

Workup

customafter purification (
washSiO2, flash elution

Sources & evidence

ORD record: ord-1b80b2b6e383475aafc4c6c1e7ada16f
Source dataset: uspto-grants-2006_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07138530B2

Reaction notes

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