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

HRID 521586Notes

Reaction equation

HRID 521586 reaction equation
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]

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-64a77280bf5548e9826ec8be33f0a565
Source dataset
uspto-grants-2016_05
Patent number
US09328114B2

Reaction notes

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