Sodium Carbonate → 4-(2-amino-5-(6-oxopiperidin-3-yl)pyridin-3-yl)-N-((S)-1-(3-chlorophenyl)-2-hydroxyethyl)-2-fluorobenzamide

HRID 595912Notes

Reaction equation

HRID 595912 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]2[CH2:13][NH:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:4][C:3]=1Br.[Cl:16][C:17]1[CH:18]=[C:19]([C@H:23]([NH:26][C:27]([C:29]2[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][C:30]=2[F:38])=[O:28])[CH2:24][OH:25])[CH:20]=[CH:21][CH:22]=1.C([O-])([O-])=O.[Na+].[Na+].S([O-])([O-])(=O)=O.[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].COCCOC>[NH2:1][C:2]1[C:3]([C:32]2[CH:33]=[CH:34][C:29]([C:27]([NH:26][C@@H:23]([C:19]3[CH:20]=[CH:21][CH:22]=[C:17]([Cl:16])[CH:18]=3)[CH2:24][OH:25])=[O:28])=[C:30]([F:38])[CH:31]=2)=[CH:4][C:5]([CH:8]2[CH2:9][CH2:10][C:11](=[O:14])[NH:12][CH2:13]2)=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 24436Sodium SulfateHCID 1180463525-(6-Amino-5-bromopyridin-3-yl)piperidin-2-oneHCID 123263941(S)-4-(1-(3-chlorophenyl)-2-hydroxyethylcarbamoyl)-3-fluorophenylboronic acid

Product 1

HCID 1180459614-(2-amino-5-(6-oxopiperidin-3-yl)pyridin-3-yl)-N-((S)-1-(3-chlorophenyl)-2-hydroxyethyl)-2-fluorobenzamide

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a microwave vial, 5-(6-amino-5-bromopyridin-3-yl)piperidin-2-one (45 mg, 0.167 mmol), (S)-(4-((1-(3-chlorophenyl)-2-hydroxyethyl)carbamoyl)-3-fluorophenyl)boronic acid (56.2 mg, 0.167 mmol), PdCl2(dppf) (12.19 mg, 0.017 mmol), DME (1111 μl, Ratio: 2.000), and Na2CO3 (2M solution) (555 μL, Ratio: 1.000) were added. The reaction mixture was heated at microwave reactor for 10 min at 120° C. LCMS—0.58 min, MH+483.2; 0.85 min, MH+613.3. After anhydrous sodium sulfate were added to remove water, the reaction mixture was filtered off and dried in vacuo. The small portion was purified by prep HPLC yielding 4-(2-amino-5-(6-oxopiperidin-3-yl)pyridin-3-yl)-N—((S)-1-(3-chlorophenyl)-2-hydroxyethyl)-2-fluorobenzamide as a diastereomeric mixture (12%). LCMS (m/z): 483.3 (MH+), 0.56 min; 1H NMR (400 MHz, CD3OD) δ ppm 7.89 (m, 1H), 7.80 (m, 2H), 7.42-7.30 (m, 3H), 7.30-7.24 (m, 2H), 7.25-7.15 (m, 1H), 5.18-5.03 (m, 1H), 3.87-3.64 (m, 2H), 3.47-3.35 (m, 2H), 3.11-2.97 (m, 1H), 2.46-2.30 (m, 2H), 2.08-1.91 (m, 2H).

Workup

  1. custom0.58 min, MH
  2. custom0.85 min, MH
  3. customto remove water
  4. filtrationthe reaction mixture was filtered off
  5. customdried in vacuo
  6. customThe small portion was purified by prep HPLC

Sources & evidence

ORD record
ord-e63e675ca6bb4634b6cbc00c7cc92996
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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