Picolinic acid → HCID 59463234, compound

HRID 1712964Notes

Reaction equation

HRID 1712964 reaction equation
[NH2:1][CH2:2][C:3]1[S:7][C:6]([C:8]([N:10]2[CH:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[OH:21])[CH2:13][C:12]([C:22]3[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=3)=[N:11]2)=[O:9])=[CH:5][CH:4]=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C.[N:48]1[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=1[C:54](O)=[O:55]>C(Cl)Cl.O>[OH:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[CH:14]1[N:10]([C:8]([C:6]2[S:7][C:3]([CH2:2][NH:1][C:54]([C:49]3[CH:50]=[CH:51][CH:52]=[CH:53][N:48]=3)=[O:55])=[CH:4][CH:5]=2)=[O:9])[N:11]=[C:12]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)[CH2:13]1

Participants

7

Reactant 4

HCID 1018Picolinic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 59463356HCID 59463356, compound

Product 1

HCID 59463234HCID 59463234, compoundYield 32.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(1-{[5-(aminomethyl)-2-thienyl]carbonyl}-3-pyridin-3-yl-4,5-dihydro-1H-pyrazol-5-yl)phenol (0.080 g, 0.21 mmol), EDCI (0.070 g, 0.36 mmol), DIPEA (0.150 mL, 0.86 mmol), and picolinic acid (0.31 g. 0.25 mmol) in DCM (4 mL) was allowed to stir at rt overnight. The reaction mixture was diluted with water and extracted with DCM. The organic solutions were combined, washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by column chromatography to give N-[(5-{[5-(2-hydroxyphenyl)-3-pyridin-3-yl-4,5-dihydro-1H-pyrazol-1-yl]carbonyl}-2-thienyl)methyl]pyridine-2-carboxamide (I-136) (0.033 g) as a clear oil. LCMS: (FA) ES+ 484.2. 1H NMR (400 MHz, d6-DMSO) δ: 9.53-9.59 (m, 1H), 9.05-9.09 (m, 1H), 8.72-8.76 (m, 1H), 8.65-8.69 (m, 1H), 8.36-8.41 (m, 1H), 8.06-8.11 (m, 1H), 7.98-8.05 (m, 1H), 7.88 (d, 1H), 7.60-7.67 (m, 2H), 7.02-7.12 (m, 2H), 6.86-6.91 (m, 1H), 6.82 (d, 1H), 6.69 (t, 1H), 5.82 (dd, 1H), 4.70 (d, 2H), 3.82-3.92 (m, 1H), and 3.17 (dd, 1H).

Workup

  1. extractionextracted with DCM
  2. washwashed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-8baa967aa8564c7aacf9edee95fceef2
Source dataset
uspto-grants-2010_09
Patent number
US07795249B2

Reaction notes

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