Hydrochloric Acid → HCID 67107840, compound

HRID 1623862

Reaction equation

HRID 1623862 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][O:10][C:11]1[CH:20]=[CH:19][C:18]([C:21]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)=[O:22])=[CH:17][C:12]=1[C:13](OC)=[O:14].[OH-].[Li+].Cl.C(N(C(C)C)CC)(C)C.[F:41][C:42]1[C:47]([NH2:48])=[CH:46][CH:45]=[CH:44][N:43]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O1CCCC1.O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][O:10][C:11]1[CH:20]=[CH:19][C:18]([C:21]([N:23]2[CH2:24][CH2:25][O:26][CH2:27][CH2:28]2)=[O:22])=[CH:17][C:12]=1[C:13]([NH:48][C:47]1[C:42]([F:41])=[N:43][CH:44]=[CH:45][CH:46]=1)=[O:14]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 27628162-Fluoropyridin-3-amineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67107388HCID 67107388, compound

Product 1

HCID 67107840HCID 67107840, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of methyl 2-([(2,4-difluorophenyl)methyl]oxy}-5-(4-morpholinylcarbonyl)benzoate (may be prepared as described in Description 110, 100 mg, 0.26 mmol) in tetrahydrofuran (THF) (4 ml) was added lithium hydroxide (26 mg, 1.09 mmol) and water (1 ml). The mixture was heated at 50° C. for one hour, cooled and 2M hydrochloric acid (0.54 ml, 1.09 mmol) was added. The solvent removed in vacuo and the residue was redissolved in N,N-dimethylformamide (4 ml). Diisopropylethylamine (0.09 ml, 0.51 mmol), 2-fluoro-3-pyridinamine (34.4 mg, 0.31 mmol) and HATU (243 mg, 0.64 mmol) were added and the mixture stirred overnight. The solvent was removed in vacuo and the residue purified by column chromatography (silicon, 10% methanol/dichloromethane) to give an oil. Purification by MDAP yielded the title compound as an off-white solid. 22 mg.

Workup

  1. temperaturecooled
  2. customThe solvent removed in vacuo
  3. dissolutionthe residue was redissolved in N,N-dimethylformamide (4 ml)
  4. customThe solvent was removed in vacuo
  5. customthe residue purified by column chromatography (silicon, 10% methanol/dichloromethane)
  6. customto give an oil
  7. customPurification by MDAP

Sources & evidence

ORD record
ord-278cab789efb4dc38f1e3025da30b0de
Source dataset
uspto-grants-2014_07
Patent number
US08778939B2

Linked notes

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