Sodium Bicarbonate → HCID 44194662, compound

HRID 1192938Notes

Reaction equation

HRID 1192938 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5](=[O:8])[NH:6][CH:7]=1.[OH:9][C:10]([CH3:43])([CH3:42])[CH2:11][C@:12]1([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH2:17][CH2:16][N:15]([C@H:18]([C:20]2[CH:25]=[CH:24][C:23](B3OC(C)(C)C(C)(C)O3)=[CH:22][CH:21]=2)[CH3:19])[C:14](=[O:35])[CH2:13]1.C([O-])(O)=O.[Na+]>COCCOC.CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:9][C:10]([CH3:43])([CH3:42])[CH2:11][C@:12]1([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH2:17][CH2:16][N:15]([C@H:18]([C:20]2[CH:21]=[CH:22][C:23]([C:2]3[CH:3]=[CH:4][C:5](=[O:8])[NH:6][CH:7]=3)=[CH:24][CH:25]=2)[CH3:19])[C:14](=[O:35])[CH2:13]1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 5995285-Bromo-2-hydroxypyridineHCID 58237932HCID 58237932, compound

Product 1

HCID 44194662HCID 44194662, compoundYield 20.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-bromopyridin-2(1H)-one (30 mg, 0.17 mmol) in DME (6 mL) was added Pd(PPh3)4 (10 mg, 0.01 mmol) under N2. The mixture was stirred at rt for 1 h. (R)-4-(2-hydroxy-2-methylpropyl)-4-phenyl-1-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)piperidin-2-one (25 mg, 0.05 mmol) in EtOH (2 mL) was added, followed by satd aq NaHCO3 (2 mL). The mixture was stirred at 100° C. for another 2 h under N2. The reaction was quenched with H2O, and extracted with EtOAc (3×). The combined organic phase was dried and concentrated to give the crude final product, which was purified by preparative TLC to give 5-(4-((S)-1-((R)-4-(2-hydroxy-2-methylpropyl)-2-oxo-4-phenylpiperidinyl)ethyl)phenyl)pyridin-2(1H)-one (4.5 mg, 20%). LC-MS Method 2 tR=1.034 min, m/z=445.2; 1H NMR (CDCl3): δ 0.86 (s, 3H), 1.02 (s, 3H), 1.41 (d, 3H), 1.82 (d, 2H), 2.00 (m, 2H), 2.11 (m, 2H), 2.62 (d, 1H), 2.85 (m, 1H), 3.42 (d, 1H), 6.0 (m, 1H), 6.69 (m, 1H), 6.88 (m, 2H), 7.09 (m, 2H), 7.17 (m, 1H), 7.25 (m, 4H), 7.51 (m, 1H), 7.78 (m, 1H).

Workup

  1. additionwas added
  2. customThe reaction was quenched with H2O
  3. extractionextracted with EtOAc (3×)
  4. customThe combined organic phase was dried
  5. concentrationconcentrated
  6. customto give the crude final product, which
  7. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-7f3dc9b404574d45a203c01f3922816b
Source dataset
uspto-grants-2014_03
Patent number
US08680281B2

Reaction notes

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