Hydrochloric Acid → N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(imino(morpholino)methyl)benzamide

HRID 633334Notes

Reaction equation

HRID 633334 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:18])[C:10]2[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=2)=[CH:4][C:3]=1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1.Cl.ClC1C=CC(NC(C2C=CC(C(=N)OCC)=CC=2)=O)=CC=1C1C=CC=CN=1.[NH:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1>C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:18])[C:10]2[CH:11]=[CH:12][C:13]([C:16](=[NH:17])[N:53]3[CH2:58][CH2:57][O:56][CH2:55][CH2:54]3)=[CH:14][CH:15]=2)=[CH:4][C:3]=1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 8083MorpholineHCID 66877087HCID 66877087, compoundHCID 66877347N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-cyanobenzamide

Product 1

HCID 58614749N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(imino(morpholino)methyl)benzamideYield 7.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Conditions

Temperature
75 °C

Procedure

N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-cyanobenzamide (300 mg, 0.899 mmol) was slurried in 45 ml ethanol and treated with 10 ml of ethanol saturated with HCl. The reaction was stored at 0° C. for 3 days, then heated to 75° C. for 3.0 hours, and cooled to room temperature for 18 hours. The reaction was cooled in an ice bath, and saturated with HCl gas. After storing at 0° C. for an additional 3 days, N2 gas was bubbled through the solution for 1.0 hour, and the solution was diluted with enough ethanol to make a 0.0155 M solution of ethyl 4-(4-chloro-3-(pyridin-2-yl)phenylcarbamoyl)benzimidate. Ethyl 4-(4-chloro-3-(pyridin-2-yl)phenylcarbamoyl)benzimidate (17.5 ml of a 0.0155 M ethanol solution, 0.27 mmol) was treated with morpholine (1.0 ml, 11.4 mmol) for 3 days. The ethanol was evaporated, and the residue purified by reverse phase HPLC to afford 30 mg of N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(imino(morpholino)methyl)benzamide. MS (Q1) 421 (M)+.

Workup

  1. temperaturecooled to room temperature for 18 hours
  2. temperatureThe reaction was cooled in an ice bath
  3. waitAfter storing at 0° C. for an additional 3 days
  4. customN2 gas was bubbled through the solution for 1.0 hour
  5. additionthe solution was diluted with enough ethanol
  6. customThe ethanol was evaporated
  7. customthe residue purified by reverse phase HPLC

Sources & evidence

ORD record
ord-1263c4f599dc4f7690ba5530c1de6c61
Source dataset
uspto-grants-2016_04
Patent number
US09321761B2

Reaction notes

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