Phosphorus oxychloride → 4-(3-chloroanilino)-6-cyano-7H-pyrrolo[2,3-d]pyrimidine

HRID 567763Notes

Reaction equation

P(Cl)(Cl)(Cl)=O.[NH2:6][C:7]([C:9]1[NH:25][C:12]2[N:13]=[CH:14][N:15]=[C:16]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=3)[C:11]=2[CH:10]=1)=O.C([O-])(O)=O.[Na+]>CN(C)C(=O)C>[Cl:24][C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][CH:21]=1)[NH:17][C:16]1[C:11]2[CH:10]=[C:9]([C:7]#[N:6])[NH:25][C:12]=2[N:13]=[CH:14][N:15]=1

Participants

Conditions

Temperature: 100 °C

Procedure

13 ml of phosphorus oxychloride are added to 1.048 g (3.6 mmol) of 6-aminocarbonyl-4-(3-chloroanilino)-7H-pyrrolo[2,3-d]pyrimidine (see Stage 10.1) and 0.7 ml of N,N-dimethylacetamide. After stirring at RT for 1 h and at 100° C. for 4 h, the reaction mixture is poured into an ice-cooled saturated solution of NaHCO3. Extraction with ethyl acetate (3 times), washing the organic layers with saturated NaHCO3 solution, water and saturated sodium chloride solution, drying (Na2SO4) and concentrating leads to a solid. Column chromatography (SiO2; ethyl acetate), and stirring the crude product in diethyl ether and hexane yields 4-(3-chloroanilino)-6-cyano-7H-pyrrolo[2,3-d]pyrimidine; m.p. 284-287° C.; TLC-Rf=0.71 (CH2Cl2/methanol [10:1]);HPLC: tRet(Grad20)=11.8.

Workup

extractionExtraction with ethyl acetate (3 times)
washwashing the organic layers with saturated NaHCO3 solution, water and saturated sodium chloride solution
dry with materialdrying (Na2SO4)
concentrationconcentrating leads to a solid
stirringColumn chromatography (SiO2; ethyl acetate), and stirring the crude product in diethyl ether and hexane

Sources & evidence

ORD record: ord-e122584d8f8a4b5a9e6870d4be2a1417
Source dataset: uspto-grants-2001_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06180636B2

Reaction notes

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