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

HRID 2216148

反応式

HRID 2216148 の反応式
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]

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 312751,4-Dioxane溶媒HCID 21863594Toluene ethanol溶媒

実験手順

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+).

後処理

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

出典と根拠

ORDレコード
ord-d8553d3df4534384aa86c4605eace347
出典データセット
uspto-grants-2006_09
特許番号
US07109354B2

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