Water → HCID 118483144, compound

HRID 1773346Notes

Reaction equation

HRID 1773346 reaction equation
[CH3:1][O:2][C:3](=[O:28])[CH2:4][N:5]1[C:10](=[O:11])[C:9]([Cl:12])=[C:8](Cl)[N:7]=[C:6]1[N:14]1[CH2:19][CH2:18][CH:17]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16][CH2:15]1.[C:29]([C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][C:32]=1[F:40])#[N:30].C([O-])([O-])=O.[Na+].[Na+].O>CN(C=O)C.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>[CH3:1][O:2][C:3](=[O:28])[CH2:4][N:5]1[C:10](=[O:11])[C:9]([Cl:12])=[C:8]([C:34]2[CH:35]=[CH:36][C:31]([C:29]#[N:30])=[C:32]([F:40])[CH:33]=2)[N:7]=[C:6]1[N:14]1[CH2:19][CH2:18][CH:17]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:25])[CH3:26])=[O:22])[CH2:16][CH2:15]1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 118483098HCID 118483098, compound

Product 1

HCID 118483144HCID 118483144, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of [2-(4-tert-butoxycarbonylamino-piperidin-1-yl)-4,5-dichloro-6-oxo-6H-pyrimidin-1-yl]-acetic acid methyl ester (5.76 g, 13.2 mmol), 4-cyano-3-fluoro benzeneboronic acid (2.24 g, 16.1 mmol), Pd(PPh3)4 (306 mmol, 0.26 mmol) and Na2CO3 (2.8 g, 26.5 mmol) in DMF:H2O (50 mL:10 mL) was stirred at 65° C. overnight under nitrogen atmosphere. The reaction mixture was concentrated, and the residue was purified by silica chromatography (1:20 to 1:0, EA:PE) to give 2.4 g of the title product (43%). 1H NMR (400 MHz, CDCl3): δ 1.27-1.37 (m, 2H), 1.45 (s, 9H), 1.99-2.02 (m, 2H), 2.99-3.06 (m, 2H), 3.68-3.76 (m, 1H), 3.78 (s, 3H), 4.42-4.52 (m, 3H), 4.90 (s, 2H), 7.63-7.66 (m, 1H), 7.67-7.71 (m, 2H). [M+H] Calc'd for C24H27ClFN5O5, 520. Found, 520.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was purified by silica chromatography (1:20 to 1:0, EA:PE)

Sources & evidence

ORD record
ord-d346332822994eada9fa65e19fff7737
Source dataset
uspto-grants-2016_02
Patent number
US09255097B2

Reaction notes

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