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

HRID 2216148

반응식

HRID 2216148 반응식
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]

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 312751,4-Dioxane용매HCID 21863594Toluene ethanol용매

실험 절차

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 mL) 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+).

후처리

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

출처 및 근거

ORD 기록
ord-d8553d3df4534384aa86c4605eace347
출처 데이터셋
uspto-grants-2006_09
특허 번호
US07109354B2

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