Hydrochloric Acid → 3-(3-(4-(Piperidin-1-yl)-2-(4-(3-(trifluoromethyl)benzylamino) pyridin-2-yl)phenylcarbamoyl)benzylthio)propanoic acid

HRID 625392Notes

Reaction equation

HRID 625392 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[CH:17]=[C:18]([CH:27]=[CH:28][CH:29]=3)[CH2:19][S:20][CH2:21][CH2:22][C:23]([O:25]C)=[O:24])=[O:15])=[C:9]([C:30]3[CH:35]=[C:34]([NH:36][CH2:37][C:38]4[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:47])([F:46])[F:45])[CH:39]=4)[CH:33]=[CH:32][N:31]=3)[CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].[OH-].Cl>O1CCCC1.O>[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[CH:17]=[C:18]([CH:27]=[CH:28][CH:29]=3)[CH2:19][S:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])=[O:15])=[C:9]([C:30]3[CH:35]=[C:34]([NH:36][CH2:37][C:38]4[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:46])([F:47])[F:45])[CH:39]=4)[CH:33]=[CH:32][N:31]=3)[CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 66586785Methyl 3-(3-(4-(piperidin-1-yl)-2-(4-(3-(trifluoromethyl)-benzylamino)pyridin-2-yl)phenylcarbamoyl)benzylthio)propanoate

Product 1

HCID 665867763-(3-(4-(Piperidin-1-yl)-2-(4-(3-(trifluoromethyl)benzylamino) pyridin-2-yl)phenylcarbamoyl)benzylthio)propanoic acidYield 11.9%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

Into a 50-mL round bottom flask, was placed a solution of methyl 3-(3-(4-(piperidin-1-yl)-2-(4-(3-(trifluoromethyl)-benzylamino)pyridin-2-yl)phenylcarbamoyl)benzylthio)propanoate (300 mg, 0.35 mmol, 1.00 equiv, 78%) in tetrahydrofuran/H2O (20/5 mL), and LiOH (150 mg, 10.00 equiv, 40%). The resulting solution was stirred for 2 h at room temperature. The reaction progress was monitored by LCMS. The solution was adjusted to pH 6-7 with hydrochloric acid (1 N). The resulting solution was extracted with 3×50 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of ethoxyethane. The resulting mixture was concentrated under vacuum. The crude product (250 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA to afford the product (27 mg, 10%) as a yellow oil. 1H-NMR (300 MHz, DMSO-d6, ppm) δ 13.49 (s, 1H), 10.05 (m, 1H), 8.89 (m, 1H), 8.02 (m, 1H), 7.68 (m, 4H), 7.37 (m, 5H), 7.08 (m, 1H), 6.91 (m, 2H), 6.28 (m, 1H), 3.80 (s, 2H), 3.23 (s, 4H), 2.27 (m, 2H), 1.63 (s, 6H). MS (ES, m/z): 649 [M+H]+.

Workup

  1. customInto a 50-mL round bottom flask, was placed
  2. extractionThe resulting solution was extracted with 3×50 mL of ethyl acetate
  3. washThe resulting mixture was washed with 1×20 mL of ethoxyethane
  4. concentrationThe resulting mixture was concentrated under vacuum
  5. customThe crude product (250 mg) was purified by reverse phase HPLC
  6. washeluting with a water/CH3CN gradient
  7. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-f1f2601f071548b2bf2d22838b1f4fcc
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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