Hydrochloric Acid → 3-((3-((4-(Piperidin-1-yl)-2-((2-(3-(trifluoromethyl)phenyl)pyrimidin-5-yl)-carbamoyl)phenyl)carbamoyl)benzyl)thio)propanoic acid

HRID 926768Notes

Reaction equation

HRID 926768 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](=[O:48])[NH:31][C:32]3[CH:33]=[N:34][C:35]([C:38]4[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:47])([F:46])[F:45])[CH:39]=4)=[N:36][CH:37]=3)[CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.O[Li].O.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](=[O:48])[NH:31][C:32]3[CH:37]=[N:36][C:35]([C:38]4[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:47])([F:45])[F:46])[CH:39]=4)=[N:34][CH:33]=3)[CH:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 66586920Methyl 3-(3-((4-(piperidin-1-yl)-2-((2-(3-(trifluoromethyl)phenyl)pyrimidin-5-yl)carbamoyl)phenyl)carbamoyl)-benzylthio)propanoate

Product 1

HCID 565953293-((3-((4-(Piperidin-1-yl)-2-((2-(3-(trifluoromethyl)phenyl)pyrimidin-5-yl)-carbamoyl)phenyl)carbamoyl)benzyl)thio)propanoic acidYield 80.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To methyl 3-(3-((4-(piperidin-1-yl)-2-((2-(3-(trifluoromethyl)phenyl)pyrimidin-5-yl)carbamoyl)phenyl)carbamoyl)-benzylthio)propanoate (280 mg, 0.41 mmol, 1.00 equiv) in tetrahydrofuran (8 mL) was added LiOH H2O (500 mg, 11.90 mmol, 25.00 equiv) in water (2 mL) and the resulting solution was stirred overnight at room temperature. The reaction progress was monitored by LCMS. The solution was adjusted to pH 5-6 with hydrochloric acid and then extracted with 2×20 mL of ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate, and concentrated under vacuum until about 5 mL remained. The product was then precipitated with petroleum ether and the resulting solids were collected by filtration and washed with ether. This resulted in 0.22 g (80%) of product as a yellow to green solid. 1H-NMR (400 MHz, DMSO, ppm): δ 12.24 (s, 1H), 10.92 (s, 1H), 10.91 (s, 1H), 9.27 (s, 2H), 8.64 (m, 2H), 68.06 (d, 1H), 7.89 (d, 2H), 7.75-7.80 (m, 2H), 7.47-7.53 (m, 2H), 7.39 (s, 1H), 7.25 (d, 1H), 3.83 (s, 2H) 3.24 (m, 4H), 2.58 (t, 2H), 1.67 (m, 4H). 1.58 (m, 2H). MS (ES, m/z): 664 [M+H]+.

Workup

  1. extractionextracted with 2×20 mL of ethyl acetate
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under vacuum until about 5 mL
  4. customThe product was then precipitated with petroleum ether
  5. filtrationthe resulting solids were collected by filtration
  6. washwashed with ether

Sources & evidence

ORD record
ord-788e336e1e3e4ff0b774cdf094d20bbc
Source dataset
uspto-grants-2016_03
Patent number
US09289429B2

Reaction notes

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