Pyrrolidine → HCID 24968219, compound

HRID 1712963Notes

Reaction equation

HRID 1712963 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[N:12]([C:13]([C:15]2[S:19][C:18]([C:20]3[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][CH:21]=3)=[CH:17][CH:16]=2)=[O:14])[N:11]=[C:10]([C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)[CH2:9]1.[NH:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.O.Cl>[N:30]1[CH:31]=[CH:32][CH:33]=[C:28]([C:10]2[CH2:9][CH:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[OH:1])[N:12]([C:13]([C:15]3[S:19][C:18]([C:20]4[CH:27]=[CH:26][C:23]([CH2:24][N:34]5[CH2:38][CH2:37][CH2:36][CH2:35]5)=[CH:22][CH:21]=4)=[CH:17][CH:16]=3)=[O:14])[N:11]=2)[CH:29]=1

Participants

7

Reactant 3

HCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 59463110HCID 59463110, compound

Product 1

HCID 24968219HCID 24968219, compoundYield 26.1%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(5-{[5-(2-hydroxyphenyl)-3-pyridin-3-yl-4,5-dihydro-1H-pyrazol-1-yl]carbonyl}-2-thienyl)benzaldehyde (0.205 g, 0.452 mmol) in THF (72 mL) was added pyrrolidine (0.042 mL, 0.50 mmol) and sodium triacetoxyborohydride (0.105 g, 0.497 mmol). The reaction mixture was allowed to stir at rt for 3 days. The solution was diluted with water and 1N aqueous HCl and extracted with EtOAc. The organic solutions were combined, washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography to give 2-[3-pyridin-3-yl-1-({5-[4-(pyrrolidin-1-ylmethyl)phenyl]-2-thienyl}carbonyl)-4,5-dihydro-1H-pyrazol-5-yl]phenol (I-56) (0.060 g, 0.118 mmol) as a white solid. LCMS: (FA) ES+ 509.4. 1H NMR (400 MHz, d6-DMSO) δ: 10.76-10.86 (bs, 1H), 9.74-9.82 (bs, 1H), 9.11 (s, 1H), 8.71-8.77 (m, 1H), 8.36-8.42 (m, 1H), 8.03-8.08 (m, 1H), 7.84-7.90 (m, 2H), 7.62-7.73 (m, 2H), 7.08 (t, 1H), 6.92-6.97 (m, 1H), 6.82-6.88 (m, 1H), 6.72 (t, 1H), 5.82-5.89 (m, 1H), 4.34-4.39 (m, 2H), 3.86-3.98 (m, 1H), 3.31-3.41 (m, 2H), 3.18-3.25 (m, 1H), 3.00-3.12 (m, 2H), 1.96-2.07 (m, 2H), and 1.82-1.94 (m, 2H).

Workup

  1. extractionextracted with EtOAc
  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-b5718727984d4ebca80933614d8402fd
Source dataset
uspto-grants-2010_09
Patent number
US07795249B2

Reaction notes

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