Hydrochloric Acid → 4-(2-(4-MorpholinophenylaMino)pyriMidin-4-yl)benzoic acid

HRID 589569Notes

Reaction equation

HRID 589569 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:19]=[C:18]([C:20]4[CH:30]=[CH:29][C:23]([C:24]([O:26]CC)=[O:25])=[CH:22][CH:21]=4)[CH:17]=[CH:16][N:15]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.CO.O1CCCC1.[OH-].[Li+].Cl>O>[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:19]=[C:18]([C:20]4[CH:30]=[CH:29][C:23]([C:24]([OH:26])=[O:25])=[CH:22][CH:21]=4)[CH:17]=[CH:16][N:15]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 21899815MeOH tetrahydrofuranHCID 25062762ethyl 4-(2-(4-MorpholinophenylaMino)pyriMidin-4-yl)benzoate

Product 1

HCID 579908204-(2-(4-MorpholinophenylaMino)pyriMidin-4-yl)benzoic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of ethyl 4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzoate (35.39 g, 87.6 mmol) in 3:1 methanol/tetrahydrofuran (350 mL) was treated with lithium hydroxide (4.41 g, 183.9 mmol) in water (90 mL). The mixture was heated at reflux for 2 h., cooled, concentrated and acidified with hydrochloric acid (2M, 92.5 mL, 185 mmol). The dark precipitate was filtered, washed with water, and dried under vacuum. The solid was ground to a powder with a mortar and pestle, triturated with methanol (500 mL) then filtered again to yield 4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzoic acid as a muddy solid. This material was washed with ether, air dried overnight, and ground to a fine powder with mortar and pestle. On the basis of mass recovery (34.49 g) the yield was assumed to be quantitative. 1H NMR (300 MHz, d6-DMSO) δ 9.47 (1H, s); 8.53 (1H, d, J=5.2 Hz); 8.24 (2H, d, J=8.5 Hz); 8.08 (2H, d, J=8.8 Hz), 7.66 (2H, d, J=9.1 Hz); 7.37 (1H, d, J=5.2Hz); 6.93 (2H, d, J=9.1 Hz); 3.73 (4H, m); 3.04 (4H, m). LC-ESI-MS (method C): rt 7.3 min.; m/z 377.1 [M+H]+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 2 h.
  3. temperaturecooled
  4. concentrationconcentrated
  5. filtrationThe dark precipitate was filtered
  6. washwashed with water
  7. customdried under vacuum
  8. customtriturated with methanol (500 mL)
  9. filtrationthen filtered again

Sources & evidence

ORD record
ord-462c60c492094a73be5b567686e6748f
Source dataset
uspto-grants-2016_01
Patent number
US09233934B2

Reaction notes

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