Sodium Carbonate → HCID 86680088, compound

HRID 1915883Notes

Reaction equation

HRID 1915883 reaction equation
[NH2:1][C:2]1[C:3]([C:9]([NH:11][C:12]2[CH:13]=[N:14][N:15]([CH2:31][CH:32]([F:34])[F:33])[C:16]=2[N:17]2[CH2:23][CH2:22][CH2:21][C@@H:20]([NH:24][C:25](=[O:30])[C:26]([F:29])([F:28])[F:27])[CH2:19][CH2:18]2)=[O:10])=[N:4][C:5](Br)=[CH:6][CH:7]=1.[F:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1B(O)O.C([O-])(=O)C.[K+].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.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]>[NH2:1][C:2]1[C:3]([C:9]([NH:11][C:12]2[CH:13]=[N:14][N:15]([CH2:31][CH:32]([F:34])[F:33])[C:16]=2[N:17]2[CH2:23][CH2:22][CH2:21][C@@H:20]([NH:24][C:25](=[O:30])[C:26]([F:29])([F:28])[F:27])[CH2:19][CH2:18]2)=[O:10])=[N:4][C:5]([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[F:35])=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 27343542-Fluorophenylboronic acidHCID 86680089HCID 86680089, compound2×

Product 1

HCID 86680088HCID 86680088, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolvent

Procedure

Following the procedures of Examples 101 or 112, (R)-3-amino-6-bromo-N-(1-(2,2-difluoroethyl)-5-(4-(2,2,2-trifluoroacetamido)azepan-1-yl)-1H-pyrazol-4-yl)picolinamide was prepared. In a microwave reaction tube, (R)-3-amino-6-bromo-N-(1-(2,2-difluoroethyl)-5-(4-(2,2,2-trifluoroacetamido)azepan-1-yl)-1H-pyrazol-4-yl)picolinamide (284 mg, 0.51 mmol), (2-fluorophenyl)boronic acid (215 mg, 1.54 mmol), and Pd(dppf)2Cl2 (37 mg, 0.051 mmol) were dissolved in acetonitrile (4 mL). 1.0M potassium acetate (0.77 mL, 0.77 mmol) and 1.0 M sodium carbonate (0.77 mL, 0.77 mmol) were added. The mixture was irradiated under microwave at 120° C. for 30 min. It was cooled and filtered through Celite and washed with methanol. The filtrate was concentrated and purified by flash chromatography eluting with 0 to 10% methanol in methylene chloride to give (R)-3-amino-N-(1-(2,2-difluoroethyl)-5-(4-(2,2,2-trifluoroacetamido)azepan-1-yl)-1H-pyrazol-4-yl)-6-(2-fluorophenyl)picolinamide (98 mg, 33%).

Workup

  1. customwas prepared
  2. customThe mixture was irradiated under microwave at 120° C. for 30 min
  3. temperatureIt was cooled
  4. filtrationfiltered through Celite
  5. washwashed with methanol
  6. concentrationThe filtrate was concentrated
  7. custompurified by flash chromatography
  8. washeluting with 0 to 10% methanol in methylene chloride

Sources & evidence

ORD record
ord-42172b981cc747fa84f195be8b1ee3e5
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

Loading…