Carbon Dioxide → HCID 86643734, compound

HRID 1959896Notes

Reaction equation

HRID 1959896 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.O1CCOCC1.N12CCCN=C1C[CH2:21][CH2:20][CH2:19][CH2:18]2.C([O:32][C:33](OC(OC(C)(C)C)=O)=[O:34])(C)(C)C.C(=O)=O>CN(C1C=CN=CC=1)C.[Cl-].[Na+].O.C(OCC)(=O)C.CCCCCC.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C:33]([O:34][CH2:18][CH2:19][CH2:20][CH3:21])=[O:32])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

10

Reactant 5

HCID 280Carbon DioxideHCID 312751,4-DioxaneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 90495Di-tert-butyl dicarbonateHCID 53566827H-Pyrrolo(2,3-d)pyrimidine, 4-chloro-

Product 1

HCID 86643734HCID 86643734, compound

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolventHCID 21226206Ethyl acetate hexaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a 250 mL round bottom flask equipped with a stir bar and nitrogen inlet was charged 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (1, 5.00 g, 0.0326 mol), 1,4-dioxane (40 ml, 0.500 mol), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 24.3 mL, 0.163 mol, 5.0 equiv) and 4-(N,N-dimethyl)aminopyridine (DMAP, 0.80 g, 0.0065 mol, 0.2 equiv). To this solution was added di-tert-butyldicarbonate (BOC2O, 21.2 g, 0.0976 mol, 3.0 equv) in one portion at room temperature. The resulting reaction solution becomes yellow/orange in color with the evolution of carbon dioxide. The reaction was monitored by TLC (80% hexane/ethyl acetate) and was complete after stirring at room temperature for about 24 hours. The reaction mixture was then diluted with 20% aqueous brine solution (40 mL) and ethyl acetate (40 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (40 mL). The combined organic extracts were washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure to yield the crude, desired product (3c) as a red to orange oil. Flash column chromatography purification (SiO2, 0 to 15% ethyl acetate/hexane gradient elution) afforded pure tent-butyl 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-7-carboxylate (3c, 6.28 g, 8.27 g theoretical, 75.9% yield) as off-white solids. For 3c: 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.79 (s, 1H), 7.94 (d, 1H, J=4.0 Hz), 6.80 (d, 1H, J=4.2 Hz), 1.60 (s, 9H); C11H12ClN3O2 (MW, 253.68), LCMS (EI) m/e 276/278 (M++Na).

Workup

  1. customTo a 250 mL round bottom flask equipped with a stir bar and nitrogen inlet
  2. customThe resulting reaction solution
  3. customThe two layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (40 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c49fac2df6d547a4bed84c288e3e7cb6
Source dataset
uspto-grants-2013_04
Patent number
US08410265B2

Reaction notes

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