Lithium hydroxide, monohydrate → 3-((3-((4-(Piperidin-1-yl)-2-(4-(3-(trifluoromethyl)benzamido)pyridin-2-yl)-phenyl)carbamoyl)benzyl)thio)propanoic acid

HRID 625402Notes

Reaction equation

HRID 625402 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][C:37](=[O:48])[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.O.[OH-].[Li+]>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][C:37](=[O:48])[C:38]4[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:47])([F:45])[F:46])[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

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 66586866Methyl 3-(3-((4-(piperidin-1-yl)-2-(4-(3-(trifluoromethyl)benzamido)-pyridin-2-yl)phenyl)carbamoyl)benzylthio)propanoate

Product 1

HCID 680873863-((3-((4-(Piperidin-1-yl)-2-(4-(3-(trifluoromethyl)benzamido)pyridin-2-yl)-phenyl)carbamoyl)benzyl)thio)propanoic acidYield 100.6%

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)benzamido)pyridin-2-yl)phenyl)carbamoyl)benzylthio)propanoate (100 mg, 0.15 mmol, 1.00 equiv) and lithium hydroxide hydrate (62.0 mg, 1.48 mmol, 10.00 equiv) in tetrahydrofuran/water (1:1) (10/10 mL). The resulting solution was stirred for 2 h at room temperature. The resulting mixture was combined with the solution of the previous batch and then concentrated under vacuum. The residual solution was adjusted to pH 5-6 with 1 N acetic acid. The resulting solution was extracted with 2×30 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate. The solvent was removed under vacuum. The crude product (140 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The fractions were collected and lyophilized to yield 100 mg (58%) of product as an off-white solid. 1H-NMR (300 MHz, DMSO-d6, ppm): δ 11.29 (br, 1H), 8.79 (d, J=6.0 Hz, 1H), 8.42 (s, 1H), 8.31-8.27 (m, 2H), 8.07-7.97 (m, 2H), 7.87-7.74 (m, 3H), 7.53-7.44 (m, 3H), 7.38-7.37 (m, 1H), 3.83 (s, 2H), 3.35 (s, 4H), 2.56 (t, J=6.3 Hz, 2H), 1.74-1.61 (m, 6H). MS (ES, m/z): 663 [M+H]+.

Workup

  1. customInto a 50-mL round bottom flask, was placed
  2. concentrationconcentrated under vacuum
  3. extractionThe resulting solution was extracted with 2×30 mL of dichloromethane
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was removed under vacuum
  6. customThe crude product (140 mg) was purified by reverse phase HPLC
  7. washeluting with a water/CH3CN gradient
  8. additioncontaining 0.05% TFA
  9. customThe fractions were collected

Sources & evidence

ORD record
ord-4cc0f4d32e5e463fab0797c994d0ac41
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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