Ethanol → tert-butyl 2-[[3-methyl-2-[5-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonyl-3-pyridinyl]phenyl]methoxy]acetate

HRID 723092Notes

Reaction equation

HRID 723092 reaction equation
[C:1]([O:5][C:6](=[O:26])[CH2:7][O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[C:11]=1B1OC(C)(C)C(C)(C)O1)([CH3:4])([CH3:3])[CH3:2].[C:27]([O:31][C:32](=[O:53])[NH:33][C:34]([C:36]1[S:37][C:38]([S:51][CH3:52])=[C:39]([S:41]([C:44]2[CH:45]=[N:46][CH:47]=[C:48](Br)[CH:49]=2)(=[O:43])=[O:42])[CH:40]=1)=[NH:35])([CH3:30])([CH3:29])[CH3:28].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.CCOC(C)=O.C1(C)C=CC=CC=1>[C:1]([O:5][C:6](=[O:26])[CH2:7][O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[C:11]=1[C:48]1[CH:47]=[N:46][CH:45]=[C:44]([S:41]([C:39]2[CH:40]=[C:36]([C:34]([NH:33][C:32]([O:31][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:53])=[NH:35])[S:37][C:38]=2[S:51][CH3:52])(=[O:43])=[O:42])[CH:49]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 69586495[3-Methyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyloxy]-acetic acid tert-butyl esterHCID 145857652tert-butyl N-[4-[(5-bromo-3-pyridinyl)sulfonyl]-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Product 1

HCID 145857618tert-butyl 2-[[3-methyl-2-[5-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonyl-3-pyridinyl]phenyl]methoxy]acetate

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

The procedure as in Example 1: step c was followed using [3-Methyl-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyloxy]-acetic acid tert-butyl ester (252.2 mg, 0.62 mmol, Example 131: step d), {[4-(5-Bromo-pyridine-3-sulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (75.9 mg, 0.15 mmol, Example 128: step a), Pd(PPh3)4 (35 mg, 0.03 mmol), aqueous Na2CO3 (2M, 1 mL), ethanol (1 mL) and toluene (2 mL). The reaction was heated to 80° C. for 24 hours. The reaction mixture was dissolved into EtOAc and washed with brine. The organic layers were dried (MgSO4) and removal of the solvents in vacuo was followed by purification by flash column chromatography (SiO2) (30% EtOAc in hexanes) of the residue yielded the title compound (460 mg) as a brown oil. ESI-MS (m/z): Calcd. for C30H37N3O7S3: 648.2 (M+1) found: 647.9.

Workup

  1. washwashed with brine
  2. customThe organic layers were dried
  3. custom(MgSO4) and removal of the solvents in vacuo
  4. customwas followed by purification by flash column chromatography (SiO2) (30% EtOAc in hexanes) of the residue

Sources & evidence

ORD record
ord-2df6961ccc8b4b51984e60ed57441395
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

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