Bicarbonate Ion → 5-Chloro-7-cyclopentyl-2-(methylthio)-7H-pyrrolo[2,3-d]pyrimidine-6-carbaldehyde

HRID 79144Notes

Reaction equation

[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([S:15][CH3:16])[N:13]=[CH:14][C:9]=3[CH:8]=[C:7]2[CH:17]=[O:18])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:19]N1C(=O)CCC1=O.O.C(=O)(O)[O-]>CN(C=O)C>[Cl:19][C:8]1[C:9]2[CH:14]=[N:13][C:12]([S:15][CH3:16])=[N:11][C:10]=2[N:6]([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)[C:7]=1[CH:17]=[O:18]

Participants

Conditions

Temperature: 100 °C

Procedure

Compound 229 (3.10 g, 11.9 mmol) and N-chlorosuccinimide (1.74 g, 13.0 mmol) were dissolved in DMF (30 mL) and stirred at 100° C. After 1 h, the temperature of the reaction was reduced to 65° C. and 0.35 eq of NCS were added. After 30 min, the reaction contents were poured into water (10×) and saturated bicarbonate was added (300 mL). The aqueous layer was extracted with dichloromethane (3×100 mL). The combined organics were dried with sodium sulfate and concentrated in vacuo. Silica gel chromatography (gradient elution 0 to 7% ethyl acetate in hexanes) afforded 5-chloro-7-cyclopentyl-2-(methylthio)-7H-pyrrolo[2,3-d]pyrimidine-6-carbaldehyde (230) (1.37 g, 39% yield). 1H NMR (500 MHz, CDCl3) δ ppm 10.17 (s, 1 H) 8.91 (s, 1 H) 5.73-5.96 (m, 1 H) 2.63 (s, 3 H) 2.29-2.47 (m, 2 H) 1.97-2.16 (m, 4 H) 1.63-1.83 (m, 2 H) ppm.

Workup

customwas reduced to 65° C.
waitAfter 30 min
customthe reaction contents
additionwas added (300 mL)
extractionThe aqueous layer was extracted with dichloromethane (3×100 mL)
dry with materialThe combined organics were dried with sodium sulfate
concentrationconcentrated in vacuo
washSilica gel chromatography (gradient elution 0 to 7% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-d7dda4812c204820b4b073b89ee6e27f
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841312B2

Reaction notes

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