1,2-Dichloroethane → HCID 69216031, compound

HRID 900171Notes

Reaction equation

HRID 900171 reaction equation
[C:1]1([C:7]2[C:15]3[C:14]([NH2:16])=[N:13][CH:12]=[N:11][C:10]=3[NH:9][C:8]=2[Si:17]([CH2:22][CH3:23])([CH2:20][CH3:21])[CH2:18][CH3:19])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH2:38]([O:40][CH:41]([O:45][CH2:46][CH3:47])[C:42](O)=[O:43])[CH3:39].[H-].[H-].[H-].[H-].[Li+].[Al+3].C1COCC1>CN(C=O)C.C(OCC)(=O)C.ClCCl>[CH2:38]([O:40][CH:41]([O:45][CH2:46][CH3:47])[C:42]([NH:16][C:14]1[C:15]2[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[C:8]([Si:17]([CH2:20][CH3:21])([CH2:22][CH3:23])[CH2:18][CH3:19])[NH:9][C:10]=2[N:11]=[CH:12][N:13]=1)=[O:43])[CH3:39]

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 8028TetrahydrofuranHCID 757711-HydroxybenzotriazoleHCID 30175042,2-diethoxyacetic acidHCID 21226445Aluminium lithium hydrideHCID 58603334HCID 58603334, compound

Product 1

HCID 69216031HCID 69216031, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-phenyl-6-(triethylsilyl)-7-H-pyrrolo[2,3-d]pyrimidin-4-amine (Example 5, Step C, 0.45 g, 1.38 mmol), EDC (0.34 g, 1.78 mmol) and HOBT (0.28 g, 2.07 mmol) in DMF (10.0 mL) was added 2,2-diethoxy acetic acid (0.25 g, 14.8 mmol) and the reaction mixture was stirred at rt for 16 h. Dichloromethane (50 mL) was added and the mixture was washed with brine, sat. NaHCO3 solution and brine. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated. The product was dissolved in 5 mL of THF and slowly added to a 11 mL of a 1 M solution of LiAlH4 in THF (11 mmol) (40 mL) at 0° C. under N2. The temperature of the reaction mixture was allowed to rise to room temperature for 1 hr after addition. The mixture was carefully poured into ice-water (50 mL). Ethyl acetate (50 mL) was added, and the organic layer was separated. The aqueous layer was extracted several times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the filtrate was concentrated. The residue was purified by chromatography on silica gel (CH2Cl2:MeOH=95:5) to give the title compound. 1H-NMR (400 MHz, DMSO-d6) δ 0.58 (q, 6H, 7.50 Hz), 0.79 (t, 9H, J=8.00 Hz), 1.04 (t, 6H, J=7.00 Hz), 3.40-3.33 (m, 2H), 3.53-3.46 (m, 4H), 4.43 (t, 1H, J=5.50 Hz), 4.84 (t, 1H, J=5.50 Hz), 7.50-7.37 (m, 5H), 8.19 (s, 1H), 11.5 (s, 1H). Mass Spectrum (ESI) m/e=441 (M+1).

Workup

  1. washthe mixture was washed with brine, sat. NaHCO3 solution and brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated
  5. dissolutionThe product was dissolved in 5 mL of THF
  6. waitto rise to room temperature for 1 hr
  7. additionafter addition
  8. customthe organic layer was separated
  9. extractionThe aqueous layer was extracted several times with ethyl acetate
  10. washThe combined organic layers were washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationthe filtrate was concentrated
  14. customThe residue was purified by chromatography on silica gel (CH2Cl2:MeOH=95:5)

Sources & evidence

ORD record
ord-043786727c1b4298bbc8b1de04c6cae1
Source dataset
uspto-grants-2008_04
Patent number
US07358250B2

Reaction notes

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