Formaldehyde → 4-Chloro-6,7,8,9-tetrahydro-5H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carboxylic acid methyl ester
Reaction equation
[CH3:1][O:2][C:3](=[O:17])[CH:4]([NH2:16])[CH2:5][C:6]1[C:14]2[C:9](=[N:10][CH:11]=[CH:12][C:13]=2[Cl:15])[NH:8][CH:7]=1.[CH2:18]=O>N1C=CC=CC=1>[CH3:1][O:2][C:3]([CH:4]1[NH:16][CH2:18][C:7]2[NH:8][C:9]3[N:10]=[CH:11][CH:12]=[C:13]([Cl:15])[C:14]=3[C:6]=2[CH2:5]1)=[O:17]Participants
Conditions
- Temperature
- 100 °C
Procedure
A suspension of 2-amino-3-(4-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-propionic acid methyl ester (3.5 g, 10 mmol) in pyridine (25 mL) was treated with formaldehyde solution (37% in water, 0.90 mL) and the resulting mixture was heated to 100° C. for 1.25 hours. The mixture was allowed to cool to ambient temperature then evaporated in-vacuo. The resultant residue was treated with saturated aqueous sodium carbonate solution (15 mL) and the resultant solid collected by filtration and washed with water (20 mL). The filtrate was extracted with 20% methanol in dichloromethane (6×25 mL). The combined organic phase was combined with solid and concentrated in-vacuo to afford the title compound as a brown residue (2.1 g, 87%). LCMS (Method B): RT=2.36 min, M+H+=266. 1H NMR (400 MHz, DMSO-d6): 11.66 (s, 1H), 8.02 (d, J=5.2 Hz, 1H), 7.06 (d, J=5.1 Hz, 1H), 4.01-3.71 (m, 3H), 3.69 (s, 3H), 3.19 (dd, J=15.4, 4.7 Hz, 1H), 2.94 (dd, J=15.4, 8.9 Hz, 1H).
Workup
- temperatureto cool to ambient temperature
- customthen evaporated in-vacuo
- additionThe resultant residue was treated with saturated aqueous sodium carbonate solution (15 mL)
- filtrationthe resultant solid collected by filtration
- washwashed with water (20 mL)
- extractionThe filtrate was extracted with 20% methanol in dichloromethane (6×25 mL)
- concentrationconcentrated in-vacuo
Sources & evidence
- ORD record
- ord-589d6f0932ab428d9a2b17c92e51079c
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09440976B2
Reaction notes
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