1,2-Dichloroethane → HCID 71470591, compound

HRID 900166Notes

Reaction equation

HRID 900166 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.[O:38]1[CH2:42][CH2:41][CH2:40][C@H:39]1[C:43](O)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>CN(C1C=CN=CC=1)C.CN(C=O)C.C1COCC1.ClCCl>[C:1]1([C:7]2[C:15]3[C:14]([NH:16][CH2:43][C@@H:39]4[CH2:40][CH2:41][CH2:42][O:38]4)=[N:13][CH:12]=[N:11][C:10]=3[NH:9][C:8]=2[Si:17]([CH2:20][CH3:21])([CH2:22][CH3:23])[CH2:18][CH3:19])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

10

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 446666Tetrahydro-2-furoic acid, (-)-HCID 21226445Aluminium lithium hydrideHCID 58603334HCID 58603334, compound

Product 1

HCID 71470591HCID 71470591, compound

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a slurry of 4.00 g (12.3 mmol) of 5-phenyl-6-(triethylsilyl)-7-H-pyrrolo[2,3-d]pyrimidin-4-amine, 3.10 g (16.0 mmol) of EDC and 2.50 g (18.5 mmol) of HOBt and catalytic DMAP in 20 ml DMF was added dropwise 1.91 g (14.8 mmol) of (S)-tetrahydro-2-furoic acid at 0° C. The reaction mixture was stirred at 0° C. for 1 h, then was warmed to room temperature and stirred for 30 h. Dichloromethane (500 ml) was added and the mixture was washed with brine (1×), saturated aqueous sodium bicarbonate (1×), and brine (1×). The organic layer was dried over Na2SO4 and filtered. The crude amide was dissolved in 20 ml THF and added to a solution of 700 mg (27.1 mmol) of lithium aluminum hydride in 40 ml THF at 0° C. The slurry was warmed to room temperature and stirred for 1 h, and then to 50° C. and stirred for an additional 2 h. The reaction mixture was cooled to room temperature and poured into ice water. The aqueous material was extracted with ethyl acetate (4×). The combined organic layers were washed with brine (1×), dried over Na2SO4, filtered and purified by chromatography on silica gel (EtOAc:MeOH:Et3N, 9:1:0.1) to give the title compound. 1H-NMR (400 MHz, CDCl3)δ, 0.61 (q, J=7.6 Hz, 6 H), 0.89 (t, J=7.6 Hz, 9 H), 1.48 (m, 1 H), 1.69-1.85 (m, 3 H), 3.59-3.62 (m, 4 H), 3.94 (m, 1 H), 5.03 (s, 1 H), 7.28 (m, 3 H), 7.45 (m, 2 H), 8.33 (s, 1 H), 8.68 (s, 1 H). Mass Spectrum (ESI) m/e=409.1 (M+1).

Workup

  1. temperaturewas warmed to room temperature
  2. stirringstirred for 30 h
  3. washthe mixture was washed with brine (1×), saturated aqueous sodium bicarbonate (1×), and brine (1×)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. dissolutionThe crude amide was dissolved in 20 ml THF
  7. temperatureThe slurry was warmed to room temperature
  8. stirringstirred for 1 h
  9. stirringto 50° C. and stirred for an additional 2 h
  10. temperatureThe reaction mixture was cooled to room temperature
  11. extractionThe aqueous material was extracted with ethyl acetate (4×)
  12. washThe combined organic layers were washed with brine (1×)
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. custompurified by chromatography on silica gel (EtOAc:MeOH:Et3N, 9:1:0.1)

Sources & evidence

ORD record
ord-d8bd987ad3aa46b8a40b3aba8d141d9e
Source dataset
uspto-grants-2008_04
Patent number
US07358250B2

Reaction notes

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