Sodium Carbonate → HCID 118045198, compound

HRID 595806Notes

Reaction equation

HRID 595806 reaction equation
Br[C:2]1[CH:19]=[CH:18][C:5]([C:6]([NH:8][C@@H:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:10][OH:11])=[O:7])=[C:4]([F:20])[CH:3]=1.[NH2:21][C:22]1[N:27]=[CH:26][C:25]([CH:28]2[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]2)=[CH:24][C:23]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C(OCC)(=O)C>[NH2:21][C:22]1[C:23]([C:2]2[CH:19]=[CH:18][C:5]([C:6]([NH:8][C@@H:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH2:10][OH:11])=[O:7])=[C:4]([F:20])[CH:3]=2)=[CH:24][C:25]([CH:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[CH:26][N:27]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 103945025HCID 103945025, compoundHCID 123183176HCID 123183176, compound

Product 1

HCID 118045198HCID 118045198, compoundYield 20.9%

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a suspension of (S)-4-bromo-2-fluoro-N-(2-hydroxy-1-phenylethyl)benzamide (67.1 mg, 0.20 mmol) in DME (5 mL) was added tert-butyl 4-(6-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)piperidine-1-carboxylate (40 mg, 0.099 mmol) and sodium carbonate (0.24 mL, 0.49 mmol). The mixture was purged with nitrogen for 10 min, then PdCl2(dppf)-CH2Cl2Adduct (12.15 mg, 0.015 mmol) was added. The reaction mixture was heated to 120° C. in an oil bath for 3 h. The reaction mixture was diluted with ethyl acetate. The organic solution was washed with water, brine, dried over sodium sulfate and concentrated. The resulting residue was treated with 30% TFA in DCM (20 mL) for 15 min. The reaction mixture was concentrated and the crude product was purified by HPLC to give (S)-4-(2-amino-5-(piperidin-4-yl)pyridin-3-yl)-2-fluoro-N-(2-hydroxy-1-phenylethyl)benzamide (9 mg, 20.8%) as TFA salt. LCMS (m/z): 435 (MH+), 0.44 min; 1H NMR (300 MHz, CD3OD) δ ppm 8.63 (br. s., 1H) 7.90 (t, J=7.77 Hz, 1H) 7.84 (s, 2H) 7.47-7.24 (m, 7H), 5.27-5.17 (m, 1H) 3.93-3.79 (m, 2H) 3.52 (d, J=12.60 Hz, 2H) 3.21-3.05 (m, 2H) 2.96 (t, J=12.31 Hz, 1H) 2.15 (d, J=14.07 Hz, 2H) 1.96-1.78 (m, 2H).

Workup

  1. customThe mixture was purged with nitrogen for 10 min
  2. washThe organic solution was washed with water, brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. additionThe resulting residue was treated with 30% TFA in DCM (20 mL) for 15 min
  6. concentrationThe reaction mixture was concentrated
  7. customthe crude product was purified by HPLC

Sources & evidence

ORD record
ord-ad833ae4670c432696c70d96d7160103
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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