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(4-Bromophenyl)boronic acid → 9-(3-(isopropylamino)propyl)-8-(6-(4-methoxyphenyl)benzo[d][1,3]dioxol-5-ylthio)-9H-purin-6-amine

HRID 521586
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HRID 521586 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([S:17][C:18]3[N:19]([CH2:28][CH2:29][CH2:30][NH:31][CH:32]([CH3:34])[CH3:33])[C:20]4[C:25]([N:26]=3)=[C:24]([NH2:27])[N:23]=[CH:22][N:21]=4)=[CH:10][C:11]3[O:15][CH2:14][O:13][C:12]=3[CH:16]=2)=[CH:4][CH:3]=1.BrC1C=CC(B(O)O)=CC=1.CC(NCCCN1C(SC2C=[C:67]3[O:69]COC3=CC=2I)=NC2C(N)=NC=NC1=2)C.C([O-])(O)=O.[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.O.CN(C=O)C>[CH:32]([NH:31][CH2:30][CH2:29][CH2:28][N:19]1[C:18]([S:17][C:9]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([O:69][CH3:67])=[CH:3][CH:4]=3)=[CH:16][C:12]3[O:13][CH2:14][O:15][C:11]=3[CH:10]=2)=[N:26][C:25]2[C:20]1=[N:21][CH:22]=[N:23][C:24]=2[NH2:27])([CH3:34])[CH3:33]
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참가 물질

8

반응물 4

HCID 79599(4-Bromophenyl)boronic acidHCID 516892Sodium BicarbonateHCID 9549213ZelavespibHCID 671167858-(6-(4-bromophenyl)benzo[d][1,3]dioxol-5-ylthio)-9-(3-(isopropylamino)propyl)-9H-purin-6-amine

생성물 1

HCID 671155379-(3-(isopropylamino)propyl)-8-(6-(4-methoxyphenyl)benzo[d][1,3]dioxol-5-ylthio)-9H-purin-6-amine

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
90 °C

실험 절차

8-(6-(4-bromophenyl)benzo[d][1,3]dioxol-5-ylthio)-9-(3-(isopropylamino)propyl)-9H-purin-6-amine [DZ3-6]. 4-Bromophenylboronic acid (17.6 mg, 0.0877 mmol) was added to PU-H71 (30 mg, 0.0585 mmol) and NaHCO3 (14.7 mg, 0.1755 mmol). DMF (1 mL) was added and the reaction mixture was evacuated and back filled with nitrogen. This was repeated four times then nitrogen was bubbled through the reaction mixture for 10 minutes. Then H2O (0.1 mL) and Pd(PPh3)2Cl2 (4 mg, 0.00584 mmol) were added and the reaction mixture was heated under nitrogen at 90° C. for 4 h. Solvent was removed under reduced pressure and the resulting residue was purified by preparatory TLC (hexane:CH2Cl2:EtOAc:MeOH—NH3 (7N), 4:5:2:1) to give 13.9 mg (44%) of DZ3-6. 1H NMR (500 MHz, CDCl3) δ 8.23 (s, 1H), 7.44 (d, J=8.2 Hz, 2H), 7.13 (d, J=8.2 Hz, 2H), 7.01 (s, 1H), 6.81 (s, 1H), 6.05 (s, 2H), 5.69 (br s, 2H), 4.08 (t, J=6.0 Hz, 2H), 2.91 (m, 1H), 2.50 (t, J=5.9 Hz, 2H), 1.98 (m, 2H), 1.20 (d, J=6.4 Hz, 6H); 13C NMR (125 MHz, CDCl3/MeOH-d4) δ 154.2, 152.0, 151.2, 149.8, 149.1, 148.2, 139.8, 139.1, 131.2, 131.0, 122.0, 119.0, 117.9, 115.0, 111.1, 102.4, 50.1, 42.1, 40.2, 27.3, 20.2; HRMS (ESI) m/z [M+H]+ calcd. for C24H26BrN6O2S, 541.1021/543.1001; found. 541.1016/543.1004; HPLC: method A Rt=6.93, method B Rt=8.30.

후처리

  1. customthe reaction mixture was evacuated
  2. additionback filled with nitrogen
  3. customnitrogen was bubbled through the reaction mixture for 10 minutes
  4. customSolvent was removed under reduced pressure
  5. customthe resulting residue was purified by preparatory TLC (hexane:CH2Cl2:EtOAc:MeOH—NH3 (7N), 4:5:2:1)
  6. customto give 13.9 mg (44%) of DZ3-6

출처 및 근거

ORD 기록
ord-64a77280bf5548e9826ec8be33f0a565
출처 데이터셋
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09328114B2

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