Sodium Carbonate → HCID 86695400, compound

HRID 1487450Notes

Reaction equation

HRID 1487450 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:12]([CH2:13][F:14])[CH:11]([C:15]2[CH:20]=[CH:19][C:18](B3OC(C)(C)C(C)(C)O3)=[CH:17][CH:16]=2)[O:10][C:9]1([CH3:31])[CH3:30])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:33]1[CH:34]=[N:35][C:36]([C:39]#[N:40])=[N:37][CH:38]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.O.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>[C:1]([O:5][C:6]([N:8]1[CH:12]([CH2:13][F:14])[CH:11]([C:15]2[CH:20]=[CH:19][C:18]([C:33]3[CH:34]=[N:35][C:36]([C:39]#[N:40])=[N:37][CH:38]=3)=[CH:17][CH:16]=2)[O:10][C:9]1([CH3:31])[CH3:30])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 6865465-Bromopyrimidine-2-carbonitrileHCID 23570604HCID 23570604, compound

Product 1

HCID 86695400HCID 86695400, compoundYield 47.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 22272177Toluene waterSolvent

Procedure

To the solution of 4-Fluoromethyl-2,2-dimethyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]oxazolidine-3-carboxylic acid tert-butyl ester (1 g, 2.298 mmol, 1.0 eq) in toluene/water (3:1-24 mL) is added 5-Bromo-pyrimidine-2-carbonitrile (0.42 g, 2.282 mmol, 1.20 eq), Na2CO3 (0.48 g, 4.528 mmol) and degassed with nitrogen for 15 minutes followed by addition of Tetrakis(triphenylphosphine)palladium(0) (0.132 g, 0.114 mmol) and heated reaction mixture to 80° C. for 16 hours. Solvent is evaporated in vacuo to get the crude which is purified by column chromatography eluting from 10% ethyl acetate/hexane to give title compound (0.45 g): 1H-NMR (400 MHz, DMSO-d6) 1.43 (s, 9H), 1.51 (s, 3H), 1.63 (s, 3H), 3.85-3.92 (m, 1H), 4.47-4.59 (m, 1H), 4.76-4.96 (m, 1H), 5.17 (d, 1H, J=7.16), 7.67 (d, 2H, J=8.24 Hz), 7.96 (d, 2H, J=8.24 Hz), 9.40 (s, 2H).). m/z M−H 410.8.

Workup

  1. customdegassed with nitrogen for 15 minutes
  2. temperatureheated
  3. customreaction mixture to 80° C. for 16 hours
  4. customSolvent is evaporated in vacuo
  5. customto get the crude which
  6. customis purified by column chromatography
  7. washeluting from 10% ethyl acetate/hexane

Sources & evidence

ORD record
ord-4fa8ab31566d4ef19b118b612a27f61b
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

Loading…