Dimethylformamide → HCID 87274774, compound

HRID 521590Notes

Reaction equation

HRID 521590 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1)=[O:2].[CH3:12][CH:13]([NH:15][CH2:16][CH2:17][CH2:18][N:19]1[C:28]([S:29][C:30]2[CH:35]=[C:34]3[O:36][CH2:37][O:38][C:33]3=[CH:32][C:31]=2I)=[N:27][C:21]2[C:22]([NH2:26])=[N:23][CH:24]=[N:25][C:20]1=2)[CH3:14].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>[NH2:26][C:22]1[N:23]=[CH:24][N:25]=[C:20]2[C:21]=1[N:27]=[C:28]([S:29][C:30]1[C:31]([C:6]3[CH:7]=[CH:8][C:3]([CH:1]=[O:2])=[CH:4][CH:5]=3)=[CH:32][C:33]3[O:38][CH2:37][O:36][C:34]=3[CH:35]=1)[N:19]2[CH2:18][CH2:17][CH2:16][NH:15][CH:13]([CH3:12])[CH3:14]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 5910734-Formylphenylboronic AcidHCID 9549213Zelavespib

Product 1

HCID 87274774HCID 87274774, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

4-Formylphenylboronic acid (13 mg, 0.0877 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 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), 2:2:1:0.5) to give 18.8 mg (66%) of DZ3-50. 1H NMR (500 MHz, MeOH-d4) δ 10.01 (s, 1H), 8.15 (s, 1H), 7.85 (d, J=8.1 Hz, 2H), 7.47 (d, J=8.1 Hz, 2H), 7.14 (s, 1H), 6.93 (s, 1H), 6.13 (s, 2H), 4.05 (t, J=6.8 Hz, 2H), 2.99 (septet, J=6.4 Hz, 1H), 2.62 (t, J=6.9 Hz, 2H), 1.99 (m, 2H), 1.24 (d, J=6.4 Hz, 6H); 13C NMR (125 MHz, MeOH-d4) δ 192.3, 154.1, 151.9, 151.0, 149.8, 148.8, 148.5, 146.4, 139.5, 135.3, 130.0, 129.4, 119.0, 117.7, 115.0, 110.8, 102.4, 49.9, 42.2, 40.3, 27.4, 20.2; HRMS (ESI) m/z [M+H]+ calcd. for C25H27N6O3S, 491.1865; found. 491.1877; HPLC: method A Rt=6.23, method B Rt=6.83.

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), 2:2:1:0.5)

Sources & evidence

ORD record
ord-e78ca4524f164e9b9173af5577233c68
Source dataset
uspto-grants-2016_05
Patent number
US09328114B2

Reaction notes

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