Methanol → 2-Amino-3-(4-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-propionic acid methyl ester hydrochloride salt

HRID 60254Notes

Reaction equation

HRID 60254 reaction equation
S(Cl)([Cl:3])=O.Cl.[NH2:6][CH:7]([CH2:11][C:12]1[C:20]2[C:15](=[N:16][CH:17]=[CH:18][C:19]=2[Cl:21])[NH:14][CH:13]=1)[C:8]([OH:10])=[O:9].[CH3:22]O>>[ClH:3].[CH3:22][O:9][C:8](=[O:10])[CH:7]([NH2:6])[CH2:11][C:12]1[C:20]2[C:15](=[N:16][CH:17]=[CH:18][C:19]=2[Cl:21])[NH:14][CH:13]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 67255739HCID 67255739, compound

Product 1

HCID 672987912-Amino-3-(4-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-propionic acid methyl ester hydrochloride saltYield 99%

Procedure

Thionyl chloride (27.5 mL) was added dropwise over 15 minutes to a cooled (0° C.) suspension of 2-amino-3-(4-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-propionic acid hydrochloride (7.28 g, 22.3 mmol) in methanol (150 mL). On complete addition, the mixture was heated under reflux for 66 hours. The mixture was allowed to cool to ambient temperature and evaporated. The resultant residue was azeotroped with toluene (2×150 mL) to afford the title compound as a fawn solid (7.7 g, 99%). 1H NMR (400 MHz, DMSO-d6): 12.06 (s, 1H), 8.39 (s, 3H), 8.17 (d, J=5.2 Hz, 1H), 7.50 (d, J=2.5 Hz, 1H), 7.19 (d, J=5.2 Hz, 1H), 4.07-4.06 (m, 1H), 3.54 (dd, J=14.9, 5.8 Hz, 1H), 3.30 (dd, J=14.9, 9.0 Hz, 1H).

Workup

  1. temperaturea cooled
  2. additionOn complete addition
  3. temperaturethe mixture was heated
  4. temperatureunder reflux for 66 hours
  5. customevaporated
  6. customThe resultant residue was azeotroped with toluene (2×150 mL)

Sources & evidence

ORD record
ord-df8003b219d64b509ecd7f8b1f3a514d
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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