Lithium hydroxide, monohydrate → 3-{6-Chloro-5-[(4,4-difluorocyclohexylmethyl)-carbamoyl]-quinolin-2-ylamino}-propionic acid

HRID 1056667Notes

Reaction equation

HRID 1056667 reaction equation
C([O:3][C:4](=[O:31])[CH2:5][CH2:6][NH:7][C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([Cl:30])[C:14]=2[C:18](=[O:29])[NH:19][CH2:20][CH:21]2[CH2:26][CH2:25][C:24]([F:28])([F:27])[CH2:23][CH2:22]2)[N:9]=1)C.O.[OH-].[Li+]>C1COCC1.O>[Cl:30][C:13]1[C:14]([C:18](=[O:29])[NH:19][CH2:20][CH:21]2[CH2:26][CH2:25][C:24]([F:27])([F:28])[CH2:23][CH2:22]2)=[C:15]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([NH:7][CH2:6][CH2:5][C:4]([OH:31])=[O:3])[CH:17]=[CH:16]2

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 1185559683-{6-Chloro-5-[(4,4-difluoro-cyclohexylmethyl)-carbamoyl]-quinolin-2-ylamino}-propionic acid ethyl ester

Product 1

HCID 1185559913-{6-Chloro-5-[(4,4-difluorocyclohexylmethyl)-carbamoyl]-quinolin-2-ylamino}-propionic acidYield 47.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-{6-Chloro-5-[(4,4-difluoro-cyclohexylmethyl)-carbamoyl]-quinolin-2-ylamino}-propionic acid ethyl ester (80 mg, 0.17 mmol, 1.00 eq) in THF (8.00 mL, 100 V) and Water (2.00 mL, 25 V) was added Lithium Hydroxide Monohydrate (14.72 mg, 0.35 mmol, 2.00 eq). The reaction mixture was stirred for overnight at room temperature. The reaction mixture was concentrated under vacuum. The aqueous solution was adjusted to pH 2 and then extracted with ethyl acetate and combined organic layer was collected and dried over anhydrous sodium sulphate, filtered, concentrated under vacuum. The crude was purified by preparative HPLC to afford the title compound (35 mg, 0.08 mmol, 45.3%) as a off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.69 (t, J=6.01 Hz, 1H), 7.60 (d, J=9.22 Hz, 1H), 7.46-7.52 (m, 2H), 7.31-7.33 (m, 1H), 6.84 (d, J=9.24 Hz, 1H), 3.57 (q, J=6.43 Hz, 2H), 3.22 (t, J=6.40 Hz, 2H), 2.54-2.57 (m, 2H), 2.03-2.00 (m, 2H), 1.72-1.89 (m, 5H), 1.22-1.31 (m, 2H). m/z: 426.0 [M+H]+

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. extractionextracted with ethyl acetate and combined organic layer
  3. customwas collected
  4. dry with materialdried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude was purified by preparative HPLC

Sources & evidence

ORD record
ord-0667c2f8bcd7483cb7769af25966d30b
Source dataset
uspto-grants-2016_07
Patent number
US09399623B2

Reaction notes

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