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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 523311
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HRID 523311 반응식
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
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참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 2

HCID 6102075Dichlorobis(triphenylphosphine)palladium촉매
HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
73 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-6716ae019c554e79b31de847b5056d56
출처 데이터셋
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09334282B2

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