Dimethylformamide → 8-(6-(furan-3-yl)benzo[d][1,3]dioxol-5-ylthio)-9-(3-(isopropylamino)propyl)-9H-purin-6-amine

HRID 521587Notes

Reaction equation

HRID 521587 reaction equation
[O:1]1[CH:5]=[CH:4][C:3](B(O)O)=[CH:2]1.[CH3:9][CH:10]([NH:12][CH2:13][CH2:14][CH2:15][N:16]1[C:25]([S:26][C:27]2[CH:32]=[C:31]3[O:33][CH2:34][O:35][C:30]3=[CH:29][C:28]=2I)=[N:24][C:18]2[C:19]([NH2:23])=[N:20][CH:21]=[N:22][C:17]1=2)[CH3:11].C([O-])(O)=O.[Na+].CN(C=O)C>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>[O:1]1[CH:5]=[CH:4][C:3]([C:28]2[C:27]([S:26][C:25]3[N:16]([CH2:15][CH2:14][CH2:13][NH:12][CH:10]([CH3:11])[CH3:9])[C:17]4[C:18]([N:24]=3)=[C:19]([NH2:23])[N:20]=[CH:21][N:22]=4)=[CH:32][C:31]3[O:33][CH2:34][O:35][C:30]=3[CH:29]=2)=[CH:2]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 2734358Furan-3-boronic acidHCID 9549213Zelavespib

Product 1

HCID 671154758-(6-(furan-3-yl)benzo[d][1,3]dioxol-5-ylthio)-9-(3-(isopropylamino)propyl)-9H-purin-6-amineYield 90.3%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

3-Furanylboronic acid (9.8 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 (CH2Cl2:MeOH—NH3 (7N), 20:1) to give 23.9 mg (90%) of DZ3-27. 1H NMR (500 MHz, CDCl3/MeOH-d4) δ 8.17 (s, 1H), 7.51 (s, 1H), 7.44 (s, 1H), 7.07 (s, 1H), 6.97 (s, 1H), 6.49 (s, 1H), 6.08 (s, 2H), 4.17 (t, J=6.9 Hz, 2H), 2.93 (septet, J=6.4 Hz, 1H), 2.64 (t, J=7.1 Hz, 2H), 2.02 (m, 2H), 1.17 (d, J=6.4 Hz, 6H); 13C NMR (125 MHz, CDCl3/MeOH-d4) δ 154.1, 151.8, 151.0, 149.7, 149.0, 147.8, 142.6, 140.4, 131.7, 124.2, 118.9, 117.8, 114.8, 111.5, 110.7, 102.1, 49.2, 42.6, 40.6, 28.0, 20.7; HRMS (ESI) m/z [M+H]+ calcd. for C22H25N6O3S, 453.1709; found. 453.1711; HPLC: method A Rt=6.18, method B Rt=6.67.

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 (CH2Cl2:MeOH—NH3 (7N), 20:1)

Sources & evidence

ORD record
ord-104086defd7b45aaba122ed70b166a96
Source dataset
uspto-grants-2016_05
Patent number
US09328114B2

Reaction notes

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