Picolinic acid → HCID 53859001, compound

HRID 863098Notes

Reaction equation

HRID 863098 reaction equation
[NH2:1][CH2:2][C:3]1[N:7]([C@H:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][C:12]([F:19])=[CH:13][C:14]=3[F:18])[CH2:9]2)[C:6](=[S:20])[NH:5][CH:4]=1.[N:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27](O)=[O:28].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C.O>[F:18][C:14]1[CH:13]=[C:12]([F:19])[CH:11]=[C:10]2[C:15]=1[CH2:16][CH2:17][C@H:8]([N:7]1[C:3]([CH2:2][NH:1][C:27](=[O:28])[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][N:21]=3)=[CH:4][NH:5][C:6]1=[S:20])[CH2:9]2

Participants

7

Reactant 4

HCID 1018Picolinic acidHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 9796181Nepicastat

Product 1

HCID 53859001HCID 53859001, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of (S)-5-aminomethyl-1-(5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)-1,3-dihydroimidazole-2-thione (295 mg, 1 mmol), prepared as in Example 31, picolinic acid (123 mg, 1 mmol) and PyBOP (620 mg, 1.2 mmol) in 10 mL of dry DMF was stirred under argon at approximately 25° C. for 5 minutes and then N,N-diisopropylethylamine (0.58 mL, 3.3 mmol) was added. The mixture was stirred for approximately 12 hours and then 10 mL of water was added. The aqueous layer was extracted with ethyl acetate (3×10 mL) and the combined extracts were washed with water, dried (MgSO4) and concentrated. The residue was purified by flash chromatography on silica gel eluting with hexane/THF (1:1 to 8:2) to give (S)-N-[3-(5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-ylmethyl]picolinamide (80 mg, 0.2 mmol), m.p. 216°-217° C.

Workup

  1. stirringThe mixture was stirred for approximately 12 hours
  2. extractionThe aqueous layer was extracted with ethyl acetate (3×10 mL)
  3. washthe combined extracts were washed with water
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on silica gel eluting with hexane/THF (1:1 to 8:2)

Sources & evidence

ORD record
ord-0e6a447532c2471b8163c437e4cdb592
Source dataset
uspto-grants-1998_02
Patent number
US05719280

Reaction notes

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