Ethyl orthoformate → HCID 57477912, compound

HRID 1467461Notes

Reaction equation

HRID 1467461 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.[CH:11](OCC)([O:15][CH2:16][CH3:17])[O:12][CH2:13][CH3:14]>>[Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([CH:11]([O:15][CH2:16][CH3:17])[O:12][CH2:13][CH3:14])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

3

Reactant 2

HCID 31214Ethyl orthoformateHCID 53566827H-Pyrrolo(2,3-d)pyrimidine, 4-chloro-

Product 1

HCID 57477912HCID 57477912, compoundYield 94%

Procedure

To a 1 liter round bottom flask equipped with a stir bar, condenser and nitrogen inlet was charged 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (1, 31.0 g, 0.202 mol) and triethyl orthoformate (330 ml, 2.00 mol, 10.0 equiv). The reaction mixture was warmed to reflux to generate a clear solution. The reaction was checked after 63 hours by HPLC. When the reaction was deemed complete, the reaction mixture was concentrated under reduced pressure. The residue was purified by a silica gel flash column chromatography eluted with a 20% to 25% ethyl acetate/hexane (v/v) gradient (TLC conditions: 30% ethyl acetate/hexane) to afford 4-chloro-7-(diethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine (3b, 48.56 g, 51.65 g theoretical, 94% yield) as a light yellow oil. For 3b: 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.68 (s, 1H), 7.79 (d, 1H, J=3.8 Hz), 6.75 (s, 1H), 6.72 (d, 1H, J=3.8 Hz), 3.68 (dd, 2H, J=9.4, 7.2 Hz), 3.54 (dd, 2H, J=9.4, 7.2 Hz), 1.11 (t, 6H, J=7.2 Hz); C11H14ClN3O2 (MW, 255.70), LCMS (EI) m/e 182/184 (M++H for corresponding 7-formylation product of 1) and 154/156 (M++H for 1).

Workup

  1. customTo a 1 liter round bottom flask equipped with a stir bar, condenser and nitrogen inlet
  2. temperatureThe reaction mixture was warmed
  3. temperatureto reflux
  4. concentrationthe reaction mixture was concentrated under reduced pressure
  5. customThe residue was purified by a silica gel flash column chromatography
  6. washeluted with a 20% to 25% ethyl acetate/hexane (v/v) gradient (TLC conditions: 30% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-2ad21424f2534bfe9021424f33cf6552
Source dataset
uspto-grants-2015_04
Patent number
US09000161B2

Reaction notes

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