Sodium Bicarbonate → 1660107-77-6

HRID 588474Notes

Reaction equation

HRID 588474 reaction equation
C([O-])(O)=[O:2].[Na+].[Cl:6][C:7]1[CH:12]=[C:11]([O:13][C:14]2[N:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[CH:10]=[CH:9][C:8]=1[C:20]1[C:29]([F:30])=[CH:28][C:27]2[N:26]=[CH:25][C:24]3[N:31]=[C:32]([CH3:48])[N:33]([C@H:34]4[CH2:39][CH2:38][N:37]([CH:40](CC=O)[C:41]([O-:43])=O)[CH2:36][C@@H:35]4[F:47])[C:23]=3[C:22]=2[CH:21]=1.CO.C(Cl)Cl>CO>[Cl:6][C:7]1[CH:12]=[C:11]([O:13][C:14]2[N:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[CH:10]=[CH:9][C:8]=1[C:20]1[C:29]([F:30])=[CH:28][C:27]2[N:26]=[CH:25][C:24]3[N:31]=[C:32]([CH3:48])[N:33]([C@H:34]4[CH2:39][CH2:38][N:37]([C:40](=[O:2])[CH2:41][OH:43])[CH2:36][C@@H:35]4[F:47])[C:23]=3[C:22]=2[CH:21]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 21226129Dichloromethane methanolHCID 131734433HCID 131734433, compound

Product 1

HCID 906471591660107-77-6Yield 81.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

NaHCO3 (11 g, 0.1309 mol) was added to a stirred solution of 2-((3S,4S)-4-(8-(2-chloro-4-(pyrimidin-2-yloxy)phenyl)-7-fluoro-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)-3-fluoropiperidin-1-yl)-2-oxoethylacetate (8 g, 0.013 mol) in MeOH (300 mL) at RT and stirred for 24 h. The reaction was monitored by TLC (5% MeOH/DCM), after completion of reaction, the reaction mixture was filtered and wand washed with MeOH (100 mL). The filtrate was concentrated to remove methanol and the residue was dissolved in DCM (200 mL) and washed with water, brine solution, dried over sodium sulphate and evaporated under vacuum. The residue was purified by column chromatography on silica gel (0-4% MeOH/DCM) to afford the 1-((3S,4S)-4-(8-(2-chloro-4-(pyrimidin-2-yloxy)phenyl)-7-fluoro-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)-3-fluoropiperidin-1-yl)-2-hydroxyethanone (6.0 g, 81% yield). Obtained solid was recrystallized in EtOH (alternatively in MeOH) 1HNMR (CDCl3, 400 MHz): δ 9.33 (s, 1H), 8.65-8.64 (d, 2H), 8.08-8.05 (d, 1H), 8.00-7.85 (m, 1H), 7.51-7.30 (m, 2H), 7.30-7.28 (dd, 1H), 7.15-7.13 (m, 1H), 5.65-5.25 (m, 1H), 4.96-4.75 (m, 1H), 4.35-4.15 (m, 2H), 3.92-3.74 (m, 2H), 3.35-3.15 (m, 1H), 3.05-2.85 (m, 2H), 2.80 (s, 3H), 2.45-2.15 (m, 2H); LCMS: 100%, m/z=565.1 (M+1); HPLC (Method-3): 99.80%, Chiral HPLC: 99.48%, rt=20.38 min., Column. AG/CHIRALPAK AD-H/03. Free Form

Workup

  1. customafter completion of reaction
  2. filtrationthe reaction mixture was filtered
  3. washwand washed with MeOH (100 mL)
  4. concentrationThe filtrate was concentrated
  5. customto remove methanol
  6. dissolutionthe residue was dissolved in DCM (200 mL)
  7. washwashed with water, brine solution
  8. dry with materialdried over sodium sulphate
  9. customevaporated under vacuum
  10. customThe residue was purified by column chromatography on silica gel (0-4% MeOH/DCM)

Sources & evidence

ORD record
ord-a28dbec3e5724164b831c8e5b44aa9b0
Source dataset
uspto-grants-2016_01
Patent number
US09227969B2

Reaction notes

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