Dabco → HCID 57707762, compound

HRID 216757Notes

Reaction equation

HRID 216757 reaction equation
Cl[C:2]1[C:3]2[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.N12CCN(CC1)CC2.[Cl:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]1[C:35]([CH:36]([OH:40])[CH2:37][CH:38]=[CH2:39])=[CH:34][C:33]2[C:28](=[C:29]([CH3:41])[CH:30]=[CH:31][CH:32]=2)[N:27]=1.[H-].[Na+]>CS(C)=O.O>[N:5]1[C:4]2[NH:8][CH:9]=[CH:10][C:3]=2[C:2]([O:40][CH:36]([C:35]2[C:26]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[Cl:19])=[N:27][C:28]3[C:33]([CH:34]=2)=[CH:32][CH:31]=[CH:30][C:29]=3[CH3:41])[CH2:37][CH:38]=[CH2:39])=[N:7][CH:6]=1

Participants

7

Reactant 4

HCID 9237DabcoHCID 24758Sodium hydrideHCID 53566827H-Pyrrolo(2,3-d)pyrimidine, 4-chloro-HCID 57707908HCID 57707908, compound

Product 1

HCID 57707762HCID 57707762, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Procedure

Prepared according to procedure L. A mixture of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (474 mg, 3.1 mmol) and 1,4-diazabicyclo[2.2.2]octane (694 mg, 6.2 mmol) in anhydrous DMSO (4.5 mL) was stirred at rt for 5 h and then added via cannula to a mixture of 1-(2-(2-chlorophenyl)-8-methylquinolin-3-yl)but-3-en-1-ol (500 mg, 1.5 mmol) and sodium hydride, 60% dispersion in mineral oil (180 mg, 4.5 mmol) in DMSO (3 mL) that had been stirred for 30 min at rt and 30 min at 50° C. prior to the addition. The mixture was stirred at rt for 6 h before addition of water (10 mL), and the mixture was extracted with EtOAc (4×20 mL). The combined organic layers were washed with water, brine, dried (MgSO4) and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: DCM/MeOH, 50/1) to provide 3-(1-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)but-3-enyl)-2-(2-chlorophenyl)-8-methyl-quinoline [PI3Kδ IC50=28 nM] as a white solid. 1H-NMR (CDCl3) δ 10.20 (s, br, 1H), 8.22 (d, J=7.5 Hz, 1H), 7.15-7.64 (m, 8H), 6.59-6.62 (m, 1H), 6.34-6.37 (m, 1H), 5.64-5.79 (m, 1H), 4.93-5.01 (m, 2H), 2.74 (t, J=8.7 Hz, 2H), 2.70 (s, 3H). Mass Spectrum (ESI) m/e=441 (M+1).

Workup

  1. customPrepared
  2. stirringhad been stirred for 30 min at rt and 30 min at 50° C.
  3. additionto the addition
  4. extractionthe mixture was extracted with EtOAc (4×20 mL)
  5. washThe combined organic layers were washed with water, brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel (eluent: DCM/MeOH, 50/1)

Sources & evidence

ORD record
ord-e8b8db8249ca4e65b5f27cd0652f0258
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

Loading…