Potassium Phosphate, Tribasic → HCID 59168280, compound

HRID 2195068Notes

Reaction equation

HRID 2195068 reaction equation
[CH2:1]([O:3][C:4](=[O:26])[C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[C:22](Cl)[N:21]=[CH:20][N:19]=3)[C@H:14]([CH3:25])[CH2:13]2)=[N:7][CH:6]=1)[CH3:2].[Cl:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][C:33]=1[F:34].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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>[CH2:1]([O:3][C:4](=[O:26])[C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[C:22]([C:30]4[CH:31]=[CH:32][C:33]([F:34])=[C:28]([Cl:27])[CH:29]=4)[N:21]=[CH:20][N:19]=3)[C@H:14]([CH3:25])[CH2:13]2)=[N:7][CH:6]=1)[CH3:2]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 59168375HCID 59168375, compound

Product 1

HCID 59168280HCID 59168280, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Bubble nitrogen through a mixture of 5-chloro-6-[4-(6-chloro-pyrimidin-4-yl)-3-(R)-methyl-piperazin-1-yl]-nicotinic acid ethyl ester (226 mg, 0.57 mmol), 3-chloro-4-fluorophenylboronic acid (99 mg, 0.57 mmol), K3PO4 (2M aqueous, 570 μL) and Pd(PPh3)4 (33 mg, 0.03 mmol) in dioxane for 10 min. Heat the mixture to 80° C. for 16 h under a nitrogen atmosphere. Cool the mixture and partition between EtOAc and water. Dry (Na2SO4) the organic layer and concentrate under reduced pressure to yield the crude product. Purify the residue with preparative plate chromatography (2×2 mm thick) using 40% EtOAc/hexanes as the eluent to afford the title compound as a foam. 1H NMR (400 MHz, CDCl3): δ1.38 (m, 6H, 2×CH3), 3.16 (m, 1H), 3.31 (dd, 1H, J=11 Hz), 3.51 (m, 1H), 4.12 (d, 1H, J=12.8 Hz), 4.21 (d, 1H, J=13 Hz), 4.39 (m, 3H), 4.77 (Br s, 1H), 6.82 (s, 1H), 7.25 (m, 1H), 7.89 (m, 1H), 8.07 (d, 1H, J=7 Hz), 8.18 (s, 1H), 8.71 (s, 1H), 8.79 (s, 1H).

Workup

  1. customBubble nitrogen
  2. temperatureCool the mixture
  3. custompartition between EtOAc and water
  4. dry with materialDry (Na2SO4) the organic layer
  5. concentrationconcentrate under reduced pressure
  6. customto yield the crude product
  7. customPurify the residue with preparative plate chromatography (2×2 mm thick)

Sources & evidence

ORD record
ord-91126d675575460497905e6a85a52ca4
Source dataset
uspto-grants-2012_12
Patent number
US08334382B2

Reaction notes

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