Formic Acid → HCID 59255422, compound

HRID 77855Notes

Reaction equation

HRID 77855 reaction equation
[CH2:1]([O:8][C:9]1[CH:28]=[CH:27][C:12]([CH2:13][C:14]2[O:18][N:17]=[C:16]([C:19]3[C:20]([NH2:26])=[N:21][CH:22]=[C:23](Cl)[CH:24]=3)[CH:15]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)=O.C(N(CC)C(C)C)(C)C.O>CN1CCCC1=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:13][C:14]2[O:18][N:17]=[C:16]([C:19]3[C:20]([NH2:26])=[N:21][CH:22]=[CH:23][CH:24]=3)[CH:15]=2)=[CH:27][CH:28]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 284Formic AcidHCID 962WaterHCID 81531DiisopropylethylamineHCID 59255519HCID 59255519, compound

Product 1

HCID 59255422HCID 59255422, compoundYield 11%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-(5-(4-benzyloxy-benzyl)-isoxazol-3-yl)-5-chloro-pyridin-2-ylamine (50 mg, 0.13 mmol) described in Manufacturing Example 29-2-3 in N-methylpyrrolidinone (2 mL) were added formic acid (7.3 μL, 0.19 mmol), N,N-diisopropylethylamine (67 μL, 0.38 mmol) and tetrakis(triphenylphosphine)palladium (0) (15 mg, 13 mmol) under nitrogen atmosphere at room temperature, which was stirred for 2 hours and 20 minutes at 100° C. Water and ethyl acetate were added to the reaction solution at room temperature, which was then filtered through a Celite pad. The filtrate was partitioned into water and ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by reverse-phase high performance liquid chromatography (using an acetonitrile-water mobile phase containing 0.1% trifluoroacetic acid) and then purified again by NH silica gel column chromatography (heptane:ethyl acetate=1:1) to obtain the title compound (5 mg, 11%).

Workup

  1. filtrationwhich was then filtered through a Celite pad
  2. customThe filtrate was partitioned into water and ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under a reduced pressure
  6. customThe residue was purified by reverse-phase high performance liquid chromatography (
  7. additioncontaining 0.1% trifluoroacetic acid) and
  8. customthen purified again by NH silica gel column chromatography (heptane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-29275e663a874972a9f0a7ab9f741692
Source dataset
uspto-grants-2014_09
Patent number
US08841327B2

Reaction notes

Loading…