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4-Chlorophenylboronic acid → 18-[4-(4'-Chloro-4-methoxybiphenyl-2-ylmethoxy)phenyl]-17-cyclohexyl-1,4,11-triazatricyclo[11.5.2.016,19]icosa-13(20),14,16(19),17-tetraene-3,12-dione

HRID 39044
ノート
印刷プレビュー

反応式

HRID 39044 の反応式
C([O-])(O)=O.[Na+].Br[C:7]1[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][C:8]=1[CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[N:34]3[C:35]4[CH:36]=[C:22]([C:23](=[O:38])[NH:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][NH:31][C:32](=[O:37])[CH2:33]3)[CH:21]=[CH:20][C:19]=4[C:18]=2[CH:39]2[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]2)=[CH:13][CH:12]=1.[Cl:51][C:52]1[CH:57]=[CH:56][C:55](B(O)O)=[CH:54][CH:53]=1>C(COC)OC.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:51][C:52]1[CH:57]=[CH:56][C:55]([C:7]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][C:8]=2[CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[N:34]4[C:35]5[CH:36]=[C:22]([C:23](=[O:38])[NH:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][NH:31][C:32](=[O:37])[CH2:33]4)[CH:21]=[CH:20][C:19]=5[C:18]=3[CH:39]3[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]3)=[CH:13][CH:12]=2)=[CH:54][CH:53]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 742994-Chlorophenylboronic acidHCID 516892Sodium BicarbonateHCID 4412925918-[4-(2-Bromo-5-methoxybenzyloxy)phenyl]-17-cyclohexyl-1,4,11-triaza-tricyclo[11.5.2.016,19]icosa-13(20),14,16(19),17-tetraene-3,12-dione

生成物 1

HCID 5954908518-[4-(4'-Chloro-4-methoxybiphenyl-2-ylmethoxy)phenyl]-17-cyclohexyl-1,4,11-triazatricyclo[11.5.2.016,19]icosa-13(20),14,16(19),17-tetraene-3,12-dione

試薬・触媒・溶媒 2

HCID 6102075Dichlorobis(triphenylphosphine)palladium触媒
HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
73 °C

実験手順

A saturated solution of NaHCO3 (1 mL) was added to a solution of 9 (20 mg, 0.029 mmol), 4-chlorobenzeneboronic acid (11 mg, 0.068 mmol) and bis(triphenyl-phosphine)palladium (II) chloride (4 mg, 0.0063 mmol) in dimethoxyethane (DME; 6 mL). The resulting solution was heated at 73° C. for 8 h. Then, the reaction mixture was successively cooled down to room temperature, partitioned between water and ethyl acetate, dried (Na2SO4) and evaporated. Purification by column chromatography (CH2Cl2/methanol, 97:3) afforded the target product contaminated with impurities. The product was further purified by trituration in methanol, then filtered off to give the target product 10: m/z=704 (M+H)+. NMR (DMSO-d6): δ (ppm) 1.23-1.33 (m, 6H), 1.42-1.53 (m, 8H), 1.67-1.77 (m, 2H), 1.87-2.02 (m, 2H), 2.80 (m, 1H, CH cyclohexyl), 3.15 (m, 4H, 2×CH2NHCO), 3.83 (s, 3H, OCH3), 4.44 (s, 2H, CH2CONH), 5.00 (s, 2H, CH2O), 7.04-7.09 (m, 3H), 7.23 (d, J=2.6 Hz, 1H), 7.29 (d, J=8.5 Hz, 1H), 7.40-7.47 (m, 7H), 7.76 (d, J=8.4 Hz, 1H), 7.93 (s, 1H), 8.30 (broad s, 1H, NH), 8.51 (broad s, 1H, NH).

後処理

  1. temperatureThen, the reaction mixture was successively cooled down to room temperature
  2. custompartitioned between water and ethyl acetate
  3. dry with materialdried (Na2SO4)
  4. customevaporated
  5. customPurification by column chromatography (CH2Cl2/methanol, 97:3)
  6. customafforded the target product
  7. customThe product was further purified by trituration in methanol
  8. filtrationfiltered off

出典と根拠

ORDレコード
ord-e104582997ac4515bc160e1926a37f5f
出典データセット
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08524716B2

反応ノート

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