Triethylamine → tert-butyl N-[4-[3-[2-methyl-4-(2-morpholin-4-ylethylamino)phenyl]phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

HRID 723193

Reaction equation

HRID 723193 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[CH:4][C:3]=1[CH3:17].CC1(C)C(C)(C)OBO1.CCN(CC)CC.[C:34]([O:38][C:39](=[O:60])[NH:40][C:41]([C:43]1[S:44][C:45]([S:58][CH3:59])=[C:46]([S:48]([C:51]2[CH:56]=[CH:55][CH:54]=[C:53](Br)[CH:52]=2)(=[O:50])=[O:49])[CH:47]=1)=[NH:42])([CH3:37])([CH3:36])[CH3:35].C([O-])([O-])=O.[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1(C)C=CC=CC=1.CCO.O1CCOCC1>[C:34]([O:38][C:39](=[O:60])[NH:40][C:41](=[NH:42])[C:43]1[S:44][C:45]([S:58][CH3:59])=[C:46]([S:48]([C:51]2[CH:56]=[C:55]([C:2]3[CH:7]=[CH:6][C:5]([NH:8][CH2:9][CH2:10][N:11]4[CH2:16][CH2:15][O:14][CH2:13][CH2:12]4)=[CH:4][C:3]=3[CH3:17])[CH:54]=[CH:53][CH:52]=2)(=[O:50])=[O:49])[CH:47]=1)([CH3:37])([CH3:35])[CH3:36]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 21886410(4-Bromo-3-methyl-phenyl)-(2-morpholin-4-yl-ethyl)-amineHCID 145857672tert-butyl N-[4-(3-bromophenyl)sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Product 1

HCID 145857609tert-butyl N-[4-[3-[2-methyl-4-(2-morpholin-4-ylethylamino)phenyl]phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamateYield 85%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolventHCID 21863594Toluene ethanolSolvent

Procedure

Following the same procedure as in Example 220, step a, reaction of (4-bromo-3-methyl-phenyl)-(2-morpholin-4-yl-ethyl)-amine (440 mg, 1.9 mmol, as prepared in Example 221, step a), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (13.3 mL, 92 mmol, Aldrich Chemical Company), PdCl2(PPh3)2 (2.2 gm, 3.1 mmol, Strem Chemicals Inc, Newburyport, Mass.), Et3N (1.6 mL, 11.4 mmol), and dioxane (5 nm) afforded 520 mg (79%) after purification (SiO2, flash elution: 30% EtOAc in hexanes) of a tan oil. ESI-MS (m/z): Calcd. for C19H31BN2O3: 347.3 (M+H); found: 347.2. The above boronate ester (520 mg, 1.5 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 (368 mg, 0.75 mmol, as prepared in Example 27, step c), tetrakis(triphenylphosine)palladium(0) (217 mg, 0.19 mmol, Strem Chemicals Inc, Newburyport, Mass.), Na2CO3 (3 mL, 2M), and toluene/EtOH mixture (2:1, 9 mL) to afford 400 mg (85%) of (imino-{4-[2′-methyl-4′-(2-morpholin-4-yl-ethylamino)-biphenyl-3-sulfonyl]-5-methylsulfanyl-thiophen-2-yl}-methyl)-carbamic acid tert-butyl ester after purification (SiO2, flash elution: EtOAc in hexanes). ESI-MS (m/z): Calcd. for C30H38N4O5S3: 630.8; found: 630.9, 531.1 (M−Boc). Treatment of this intermediate with trifluoroacetic acid and purification using C18-HPLC (as in Example 220, step c) provided 312 mg (78%) of the title compound as a white solid. 1H-NMR (CD3OD, 400 MHz): δ 8.31 (s, 1H), 7.90–7.95 (m, 2H), 7.60–7.65 (m, 2H), 7.04 (d, 1H, J=8.1 Hz), 6.61–6.66 (m, 2H), 3.95 (br s, 4H), 3.61 (t, 2H, J=6.3 Hz), 3.41 (m, 6H), 2.71 (s, 3H), 2.19 (s, 3H). ESI-MS (m/z): Calcd. for C25H30N4O3S3: 531.2 (M+H); found: 531.1, 266.2 (M2+).

Workup

  1. customafforded 520 mg (79%)
  2. customafter purification (SiO2, flash elution: 30% EtOAc in hexanes) of a tan oil

Sources & evidence

ORD record
ord-eff20673de0447e9bd96da4f967e9dec
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Linked notes

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