Dimethylformamide → 8-(6-(4-(dimethylamino)phenyl)benzo[d][1,3]dioxol-5-ylthio)-9-(3-(isopropylamino)propyl)-9H-purin-6-amine

HRID 521583Notes

Reaction equation

HRID 521583 reaction equation
[CH3:1][N:2]([CH3:12])[C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.[CH3:13][CH:14]([NH:16][CH2:17][CH2:18][CH2:19][N:20]1[C:29]([S:30][C:31]2[CH:36]=[C:35]3[O:37][CH2:38][O:39][C:34]3=[CH:33][C:32]=2I)=[N:28][C:22]2[C:23]([NH2:27])=[N:24][CH:25]=[N:26][C:21]1=2)[CH3:15].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>[CH3:1][N:2]([CH3:12])[C:3]1[CH:8]=[CH:7][C:6]([C:32]2[C:31]([S:30][C:29]3[N:20]([CH2:19][CH2:18][CH2:17][NH:16][CH:14]([CH3:15])[CH3:13])[C:21]4[C:22]([N:28]=3)=[C:23]([NH2:27])[N:24]=[CH:25][N:26]=4)=[CH:36][C:35]3[O:37][CH2:38][O:39][C:34]=3[CH:33]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 27343444-(Dimethylamino)phenylboronic acidHCID 9549213Zelavespib

Product 1

HCID 671156728-(6-(4-(dimethylamino)phenyl)benzo[d][1,3]dioxol-5-ylthio)-9-(3-(isopropylamino)propyl)-9H-purin-6-amineYield 85.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

4-(Dimethylamino)phenylboronic acid (14.5 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 3 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 25.3 mg (85%) of DZ2-392. 1H NMR (500 MHz, CDCl3) δ 8.24 (s, 1H), 7.13 (d, J=8.7 Hz, 2H), 6.93 (s, 1H), 6.83 (s, 1H), 6.67 (d, J=8.7 Hz, 2H), 6.01 (br s, 2H), 5.98 (s, 2H), 4.02 (t, J=6.7 Hz, 2H), 2.97 (s, 6H), 2.78 (septet, J=6.3 Hz, 1H), 2.44 (t, J=6.7 Hz, 2H), 1.87 (m, 2H), 1.10 (d, J=6.3 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ 154.4, 152.4, 151.5, 149.9, 148.5, 148.0, 147.1, 139.6, 130.0, 127.8, 120.5, 119.7, 112.8, 111.7, 111.0, 101.7, 49.3, 43.1, 40.9, 40.4, 28.9, 21.9; HRMS (ESI) m/z [M+H]+ calcd. for C26H32N7O2S, 506.2338; found. 506.2330; HPLC: method A Rt=5.72, method B Rt=5.12.

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)

Sources & evidence

ORD record
ord-7fa48d4b120d46f89e98fc5634b010f6
Source dataset
uspto-grants-2016_05
Patent number
US09328114B2

Reaction notes

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