Trifluoroacetic acid → HCID 69587313, compound

HRID 723197Notes

Reaction equation

HRID 723197 reaction equation
C(OC(=O)[NH:7][C:8]([C:10]1[S:11][C:12]([S:34][CH3:35])=[C:13]([S:15]([C:18]2[CH:19]=[C:20]([C:24]3[CH:29]=[CH:28][C:27]([C:30](=[O:32])[NH2:31])=[CH:26][C:25]=3[CH3:33])[CH:21]=[CH:22][CH:23]=2)(=[O:17])=[O:16])[CH:14]=1)=[NH:9])(C)(C)C.[C:37]([OH:43])([C:39]([F:42])([F:41])[F:40])=[O:38]>>[F:40][C:39]([F:42])([F:41])[C:37]([OH:43])=[O:38].[C:8]([C:10]1[S:11][C:12]([S:34][CH3:35])=[C:13]([S:15]([C:18]2[CH:19]=[C:20]([C:24]3[CH:29]=[CH:28][C:27]([C:30]([NH2:31])=[O:32])=[CH:26][C:25]=3[CH3:33])[CH:21]=[CH:22][CH:23]=2)(=[O:16])=[O:17])[CH:14]=1)(=[NH:7])[NH2:9]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 145857647HCID 145857647, compound

Product 1

HCID 69587313HCID 69587313, compoundYield 59%

Procedure

Following the same procedure as in Example 220, step a, reaction of 4-bromo-3-methyl-benzamide (200 mg, 0.93 mmol), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.41 mL, 2.8 mmol, Aldrich Chemical Company), PdCl2(PPh3)2 (65 mg, 0.093 mmol, Strem Chemicals Inc, Newburyport, Mass.), Et3N (700 μL, 46 mmol), and dioxane (5 mL) afforded 140 mg of a brown oil (58%) after purification (SiO2, flash elution: 30% EtOAc in hexanes. The above boronate ester (140 mg, 0.54 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 (88 mg, 0.18 mmol, as prepared in Example 27, step c), tetrakis(triphenylphosine)palladium(0) (52 mg, 0.05 mmol, Strem Chemicals Inc, Newburyport, Mass.), Na2CO3 (0.7 mL, 2 M), and toluene/EtOH mixture (2:1, 2.1 mL) to afford {[4-(4′-Carbamoyl-2′-methyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester after purification (preparative TLC, 1:3 EtOAc/hexanes, 3×1000μ SiO2 plate). ESI-MS (m/z): Calcd. for C25H27N3O5S3: 545.7; found: 446.1 (M−Boc). The above benzamide (44 mg. 0.08 mmol) was subjected to TFA treatment followed by C18-HPLC purification as described in Example 220, step c to afford 26 mg (59%) of the title compound as a white solid. 1H-NMR (CD3OD; 400 MHz) δ 8.33 (s, 1H), 8.04–8.08 (m, 1H), 7.99–8.01 (m, 1H), 7.85 (m, 1H), 7.78 (m, 1H), 7.70–7.73 (m, 2H), 7.32 (d, 1H, J=7.9 Hz), 2.72 (s, 3H), 2.29 (s, 3H). ESI-MS (m/z): Calcd. for C20H19N3O3S3: 446.1 (M+H); found: 446.1.

Workup

  1. customafter purification (preparative TLC, 1:3 EtOAc/hexanes, 3×1000μ SiO2 plate)
  2. customfollowed by C18-HPLC purification

Sources & evidence

ORD record
ord-bcacd2ea640f4750b8a66c88b6a2ecb1
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

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