N,N-Dimethylaniline → N-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropionamide

HRID 417833Notes

Reaction equation

HRID 417833 reaction equation
[CH3:1][C:2]([CH3:17])([CH3:16])[C:3]([NH:5][C:6]1[NH:7][C:8](=O)[C:9]2[CH:14]=[CH:13][NH:12][C:10]=2[N:11]=1)=[O:4].O=P(Cl)(Cl)[Cl:20].CN(C)C1C=CC=CC=1>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.C(#N)C>[Cl:20][C:8]1[C:9]2[CH:14]=[CH:13][NH:12][C:10]=2[N:11]=[C:6]([NH:5][C:3](=[O:4])[C:2]([CH3:17])([CH3:16])[CH3:1])[N:7]=1

Participants

6

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 135512721N-(4-Oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-2-yl)pivalamide

Product 1

HCID 11425285N-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2-dimethylpropionamideYield 70%

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 6342AcetonitrileSolvent

Procedure

A mixture of 2,2-dimethyl-N-(4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)-propionamide (210 g, 0.90 mol), POCl3 (828 g, 5.40 mol, 503 mL, 6.0 eq), benzyltriethylammonium chloride (411 g, 1.80 mol), N,N-dimethylaniline (220 g, 231 mL, 1.80 mol), and acetonitrile (2.0 L) was heated to reflux for 40-60 min, monitoring with HPLC. The solvent was evaporated on a rotary evaporator, and the residue was carefully (caution: exothermic and corrosive) and slowly added to ice water (16 L). The pH was adjusted to 7 with solid NaOH, and the resulting precipitate was collected by filtration. Drying afforded the title compound (159 g, 70% yield 70%, HPLC purity 100%). tR: 5.37 min. 1H-NMR (DMSO-d6) δ 12.35 (br. s, 1H), 10.06 (br. S, 1H), 7.54 (q, 1H), 6.52 (q, 1H), 1.25 (s, 9H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 40-60 min
  3. customThe solvent was evaporated on a rotary evaporator
  4. additionslowly added to ice water (16 L)
  5. filtrationthe resulting precipitate was collected by filtration
  6. customDrying

Sources & evidence

ORD record
ord-0e0a5e7054db44e2b1385103e0761f1c
Source dataset
uspto-grants-2012_01
Patent number
US08093229B2

Reaction notes

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