Sodium Carbonate → tert-butyl N-[4-[3-(2-amino-4-methoxy-6-methylphenyl)phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

HRID 2216124Notes

Reaction equation

HRID 2216124 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].[CH3:28][O:29][C:30]1[CH:31]=[C:32]([CH3:46])[C:33](B2OC(C)(C)C(C)(C)O2)=[C:34]([NH2:36])[CH:35]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.CCOC(C)=O.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>[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:19]=[C:20]([C:33]3[C:32]([CH3:46])=[CH:31][C:30]([O:29][CH3:28])=[CH:35][C:34]=3[NH2:36])[CH:21]=[CH:22][CH:23]=2)(=[O:17])=[O:16])[CH:14]=1)=[NH:9])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 218865585-Methoxy-3-methyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamineHCID 145857672tert-butyl N-[4-(3-bromophenyl)sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Product 1

HCID 145857653tert-butyl N-[4-[3-(2-amino-4-methoxy-6-methylphenyl)phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamateYield 40%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
80 °C

Procedure

A solution of {[4-(3-bromo-benzenesulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester ((Example 27: step c) 1.50 g, 3.05 mmol) in toluene:EtOH (2:1, 45 mL) was treated with 5-methoxy-3-methyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine (((Example 198: step d) 1.61 g, 6.11 mmol), aqueous Na2CO3 (2 M, 12.2 mL, 24.4 mmol) and Pd (PPh3)4 (0.706 g, 0.611 mmol). The mixture was heated to 80° C. 4 h. The reaction was cooled to room temperature, diluted with EtOAc, washed with brine (1×75 mL) and water (2×75 mL), dried over MgSO4 and concentrated in vacuo. Silica gel chromatography (25% then 35% then 50% EtOAc in hexanes) afforded the product {[4-(2′-amino-4′-methoxy-6′-methyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (0.680 g, 40%) as a yellow-brown solid. 1H NMR (MeOD): δ 8.223 (s, 1H), 8.001 (d, 1H, J=7.2 Hz), 7.879 (t, 1H, J=1.6 Hz), 7.698 (t, 1H, J=8.0 Hz), 7.549 (d, 1H, J=8.0 Hz), 6.287 (dd, 2H, J=7.2 Hz, J=2.4 Hz), 3.770 (s, 3H), 2.669 (s, 3H), 1.900 (s, 3H), 1.510 (s, 9H). C25H29N3O5S3: 548.13 (M+1) found 547.70.

Workup

  1. custom4 h
  2. temperatureThe reaction was cooled to room temperature
  3. washwashed with brine (1×75 mL) and water (2×75 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6eb0bcbf46ea42798fe7e38a42a6dffd
Source dataset
uspto-grants-2006_09
Patent number
US07109354B2

Reaction notes

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