Citric Acid → HCID 58334486, compound

HRID 2096304Notes

Reaction equation

HRID 2096304 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:15]=[CH:16][C:17]2[N:18]([C:20]([NH:23][C:24]([N:26]3[CH2:31][CH2:30][CH:29]([C:32]([O:34]CC)=[O:33])[CH2:28][CH2:27]3)=[O:25])=[CH:21][N:22]=2)[N:19]=1.O.[OH-].[Li+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.CO.O.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:15]=[CH:16][C:17]2[N:18]([C:20]([NH:23][C:24]([N:26]3[CH2:27][CH2:28][CH:29]([C:32]([OH:34])=[O:33])[CH2:30][CH2:31]3)=[O:25])=[CH:21][N:22]=2)[N:19]=1

Participants

6

Reactant 3

HCID 311Citric AcidHCID 168937Lithium hydroxide, monohydrateHCID 58334506HCID 58334506, compound

Product 1

HCID 58334486HCID 58334486, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

(R)-ethyl 1-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-ylcarbamoyl)piperidine-4-carboxylate (Example 31, 9.2 mg, 0.018 mmol) was dissolved in a mixture solvent of THF:MeOH:water (2:2:1 v/v; 0.2 mL), followed by addition of lithium hydroxide monohydrate (2.3 mg, 0.055 mmol). After stirring at ambient temperature overnight, the reaction was diluted with water (1 mL), acidified with 10% citric acid, and extracted with EtOAc (3×1 mL). The combined organic layers were concentrated, and the crude material was purified by reverse-phase column chromatography, eluting with 5 to 55% MeOH/water to yield the final product as a solid. MS (apci) m/z=471.2 (M+H).

Workup

  1. extractionextracted with EtOAc (3×1 mL)
  2. concentrationThe combined organic layers were concentrated
  3. customthe crude material was purified by reverse-phase column chromatography
  4. washeluting with 5 to 55% MeOH/water

Sources & evidence

ORD record
ord-ec34fa1673474d0294392a59b7834f12
Source dataset
uspto-grants-2013_05
Patent number
US08450322B2

Reaction notes

Loading…