Sodium hydride → 3-((4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)-2-(2-chlorophenyl)-8-methylquinoline

HRID 2074510Notes

Reaction equation

HRID 2074510 reaction equation
[Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[H-].[Na+].Cl[CH2:14][C:15]1[C:16]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[Cl:32])=[N:17][C:18]2[C:23]([CH:24]=1)=[CH:22][CH:21]=[CH:20][C:19]=2[CH3:25]>CN(C=O)C>[Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([CH2:14][C:15]3[C:16]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[Cl:32])=[N:17][C:18]4[C:23]([CH:24]=3)=[CH:22][CH:21]=[CH:20][C:19]=4[CH3:25])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 53566827H-Pyrrolo(2,3-d)pyrimidine, 4-chloro-HCID 575561573-(Chloromethyl)-2-(2-chlorophenyl)-8-methylquinoline

Product 1

HCID 866266223-((4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)-2-(2-chlorophenyl)-8-methylquinoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (280 mg, 1.1 eq) in DMF (3 mL) was treated with NaH (1.2 eq, 80 mg, 60%) and the reaction mixture was stirred at rt for 30 min before addition of 3-(chloromethyl)-2-(2-chlorophenyl)-8-methylquinoline (500 mg, 1.7 mmol) in DMF (2 mL). After 2 h at rt, the mixture was partitioned between EtOAc (50 mL) and H2O (30 mL), the layers were separated, and the aqueous layer was extracted with EtOAc (2×30 mL). The combined organic layers were dried (Na2SO4), concentrated and purified by flash chromatography (0% to 25% EtOAc/hexane) to provide 3-((4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl)-2-(2-chlorophenyl)-8-methylquinoline as a white foam. This material (60 mg, 0.14 mmol) was dissolved in EtOH (4 mL) and treated with NH3 gas for 3 min. The sealed tube was heated at 80° C. for 4 days. The reaction mixture was concentrated and purified by column chromatography on silica gel (eluent: DCM/MeOH, 20/1) to provide a white solid [PI3Kδ IC50=1968 nM]. 1H-NMR (DMSO-d6) δ 7.94 (s, 1H), 7.89 (s, 1H), 7.75 (t, J=7.8 Hz, 1H), 7.37-7.62 (m, 6H), 6.96 (s, 2H), 6.86 (d, J=3.6 Hz, 1H), 6.54 (d, J=3.5 Hz, 1H), 5.30 (d, J=5.9 Hz, 2H), 2.64 (s, 3H). Mass Spectrum (ESI) m/e=400 (M+1).

Workup

  1. customthe mixture was partitioned between EtOAc (50 mL) and H2O (30 mL)
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (2×30 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. concentrationconcentrated
  6. custompurified by flash chromatography (0% to 25% EtOAc/hexane)

Sources & evidence

ORD record
ord-75cfb205769747388c63d1a2354ba88d
Source dataset
uspto-grants-2011_04
Patent number
US07919498B2

Reaction notes

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