Sodium Hydroxide → (1-{5-[({5-[(3,4-Difluorophenyl)amino]-1,3,4-oxadiazol-2-yl}carbonyl)amino]pyridin-2-yl}piperidin-4-yl)acetic acid

HRID 1713775Notes

Reaction equation

HRID 1713775 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[O:14][C:13]([C:15]([NH:17][C:18]3[CH:19]=[CH:20][C:21]([N:24]4[CH2:29][CH2:28][CH:27]([CH2:30][C:31]([O:33]C)=[O:32])[CH2:26][CH2:25]4)=[N:22][CH:23]=3)=[O:16])=[N:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].[OH-].[Na+]>CO.CS(C)=O.CC#N.O>[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[O:14][C:13]([C:15]([NH:17][C:18]3[CH:19]=[CH:20][C:21]([N:24]4[CH2:25][CH2:26][CH:27]([CH2:30][C:31]([OH:33])=[O:32])[CH2:28][CH2:29]4)=[N:22][CH:23]=3)=[O:16])=[N:12][N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 59464247Methyl (1-{5-[({5-[(3,4-difluorophenyl)amino]-1,3,4-oxadiazol-2-yl}carbonyl)amino]pyridin-2-yl}piperidin-4-yl)acetate

Product 1

HCID 59464197(1-{5-[({5-[(3,4-Difluorophenyl)amino]-1,3,4-oxadiazol-2-yl}carbonyl)amino]pyridin-2-yl}piperidin-4-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 86584666DMSO MeCN waterSolvent

Procedure

To a solution of methyl (1-{5-[({5-[(3,4-difluorophenyl)amino]-1,3,4-oxadiazol-2-yl}carbonyl)amino]pyridin-2-yl}piperidin-4-yl)acetate (Example 619, 189 mg, 0.40 mmol) in MeOH (10 mL) was added a 2M solution of NaOH (1 mL). The resulting yellow solution was allowed to stir at ambient temperature overnight. The volatile organics were removed by evaporation and residue adjusted to pH ˜1 with 2M HCl and the suspension was filtered and dried to leave a solid which was dissolved in DMSO/MeCN/water(7:2:1) and purified on a reverse phase preparative HPLC column eluting 5-95% MeCN 0.2% TFA. The title compound was isolated as a yellow solid (108 mg, 0.235 mmol; 58.9%); 1H NMR δ 1.16-1.27 (m, 2H), 1.76 (d, 2H), 1.91-1.99 (m, 1H), 2.19 (d, 2H), 2.90 (t, 2H), 4.21 (d, 2H), 7.00 (br d, 1H), 7.34-7.37 (m, 1H), 7.49 (q, 1H), 7.67-7.73 (m, 1H), 7.98 (d, 1H), 8.46 (s, 1H), 11.01 (s, 1H), 11.23 (s, 1H); CO2H not seen; MS m/e MH+ 459.

Workup

  1. customThe volatile organics were removed by evaporation and residue
  2. filtrationthe suspension was filtered
  3. customdried
  4. customto leave a solid which
  5. custompurified on a reverse phase preparative HPLC column
  6. washeluting 5-95% MeCN 0.2% TFA

Sources & evidence

ORD record
ord-e18e188d1b5d4d38ae9916f54859a195
Source dataset
uspto-grants-2010_09
Patent number
US07795283B2

Reaction notes

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