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

HRID 521589Notes

Reaction equation

HRID 521589 reaction equation
[CH:1]([NH:4][CH2:5][CH2:6][CH2:7][N:8]1[C:16]([S:17][C:18]2[C:26]([C:27]3[CH:28]=[N:29]O[CH:31]=3)=[CH:25][C:21]3[O:22][CH2:23][O:24][C:20]=3[CH:19]=2)=[N:15][C:14]2[C:9]1=[N:10][CH:11]=[N:12][C:13]=2[NH2:32])([CH3:3])[CH3:2].O1C=C(B2OC(C)(C)C(C)(C)O2)[CH:35]=N1.CC(NCCCN1C(SC2C=C3OCOC3=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>[NH:29]1[CH:35]=[CH:31][C:27]([C:26]2[C:18]([S:17][C:16]3[N:8]([CH2:7][CH2:6][CH2:5][NH:4][CH:1]([CH3:3])[CH3:2])[C:9]4[C:14]([N:15]=3)=[C:13]([NH2:32])[N:12]=[CH:11][N:10]=4)=[CH:19][C:20]3[O:24][CH2:23][O:22][C:21]=3[CH:25]=2)=[CH:28]1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 9549213ZelavespibHCID 164141804-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-oxazoleHCID 671157579-(3-(isopropylamino)propyl)-8-(6-(isoxazol-4-yl)benzo[d][1,3]dioxol-5-ylthio)-9H-purin-6-amine

Product 1

HCID 671156198-(6-(1H-pyrrol-3-yl)benzo[d][1,3]dioxol-5-ylthio)-9-(3-(isopropylamino)propyl)-9H-purin-6-amineYield 28%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

9-(3-(isopropylamino)propyl)-8-(6-(isoxazol-4-yl)benzo[d][1,3]dioxol-5-ylthio)-9H-purin-6-amine [DZ3-49]. 4-Isoxazoleboronic acid pinacol ester (20.5 mg, 0.1053 mmol) was added to PU-H71 (30 mg, 0.0585 mmol) and NaHCO3 (14.7 mg, 0.1755 mmol). DMF (1.2 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 (8 mg, 0.0117 mmol) were added and the reaction mixture was heated under nitrogen at 60° C. for 4 h. Solvent was removed under reduced pressure and the resulting residue was attempted to be purified by preparatory TLC (hexane:CH2Cl2:EtOAc:MeOH—NH3 (7N), 4:7:2:1) to give 7.4 mg (28%) of an inseparable mixture of DZ3-49 and DZ3-39 in a ratio of approximately 71:29, respectively, as determined by HPLC. 1H NMR (500 MHz, CDCl3/MeOH-d4) δ 8.66 (s, 1H), 8.45 (s, 1H), 8.17 (s, 1H), 7.18 (s, 1H), 7.01 (s, 1H), 6.13 (s, 2H), 4.37 (t, J=7.0 Hz, 2H), 3.27 (septet, J=7.1 Hz, 1H), 2.89 (t, J=7.1 Hz, 2H), 2.22 (m, 2H), 1.38 (d, J=6.5 Hz, 6H); MS (ESI) m/z [M+H]+ 454.1; HPLC: method ARt=5.67 (DZ3-39, 29%) and 5.87 (DZ3-49, 71%); method B Rt=4.58 (DZ3-39, 34%) and 5.57 (DZ3-49, 66%).

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. customto be purified by preparatory TLC (hexane:CH2Cl2:EtOAc:MeOH—NH3 (7N), 4:7:2:1)

Sources & evidence

ORD record
ord-154042d87199425482dd6b4412e0b151
Source dataset
uspto-grants-2016_05
Patent number
US09328114B2

Reaction notes

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