1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-Chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (1-dimethylcarbamoyl-2-phenylethyl)amide

To a solution of 6-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (Preparation 116, 47 mg, 0.24 mmol) in DMF (5 mL, anhydrous) was added 2-(S)-amino-N,N-dimethyl-3-phenylpropionamide hydrochloride (Preparation 8, 56 mg, 0.25 mmol), DIPEA (131 μL, 0.75 mmol) and HOBt (40 mg, 0.26 mmol) sequentially. The solution was stirred for 5 min prior to the addition of EDCI (55 mg, 0.29 mmol) in one portion. The resulting solution was stirred for 12 h at rt. The reaction mixture was partitioned between ethyl acetate (50 mL) and water/brine (150 mL, 1:1). The layers were separated and the aqueous phase extracted with ethyl acetate (3×50 mL), then the combined organics were washed with dilute HCl solution (1M, 50 mL), dilute NaOH solution (1M, 50 mL) and brine (50 mL). The organic phase was dried (MgSO4), filtered and concentrated in vacuo. Purification via flash column chromatography eluting with toluene/acetone (3:1) gave the title compound. δH (CDCl3): 2.88, 3.05 (6H, 2s), 3.18, 3.28 (2H, 2 dd), 5.41 (2H, m), 7.02 (1H, s), 7.28-7.34 (6H, m), 8.17 (1H, d), 8.68 (1H, s), 10.58 (1H, br s); m/z (ES+)=371.13 [M+H]+; RT=3.28 min.

1. stirringThe resulting solution was stirred for 12 h at rt
2. customThe reaction mixture was partitioned between ethyl acetate (50 mL) and water/brine (150 mL, 1:1)
3. customThe layers were separated
4. extractionthe aqueous phase extracted with ethyl acetate (3×50 mL)
5. washthe combined organics were washed with dilute HCl solution (1M, 50 mL), dilute NaOH solution (1M, 50 mL) and brine (50 mL)
6. dry with materialThe organic phase was dried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customPurification via flash column chromatography
10. washeluting with toluene/acetone (3:1)

ORD 기록

ord-a7e5b4bd971e4e2a9d1b630be0d18b89

출처 데이터셋

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08158622B2