Sodium hydride → HCID 25152050, compound

HRID 2066825Notes

Reaction equation

HRID 2066825 reaction equation
[H-].[Na+].[C:3]([C:5]1[CH:6]=[C:7]([CH:40]([CH3:42])[CH3:41])[C:8]2[O:12][C:11]([C:13]3[CH:38]=[CH:37][C:16]([C:17]([NH:19][CH2:20][C:21]4([CH3:36])[O:25][C:24](=[O:26])[N:23](CC5C=CC(OC)=CC=5)[CH2:22]4)=[O:18])=[CH:15][CH:14]=3)=[N:10][C:9]=2[CH:39]=1)#[N:4].Cl[C:44]1[N:49]=[C:48]([C:50]([F:53])([F:52])[F:51])[CH:47]=[CH:46][N:45]=1>CN(C)C=O>[C:3]([C:5]1[CH:6]=[C:7]([CH:40]([CH3:42])[CH3:41])[C:8]2[O:12][C:11]([C:13]3[CH:38]=[CH:37][C:16]([C:17]([NH:19][CH2:20][C:21]4([CH3:36])[O:25][C:24](=[O:26])[N:23]([C:44]5[N:49]=[C:48]([C:50]([F:53])([F:52])[F:51])[CH:47]=[CH:46][N:45]=5)[CH2:22]4)=[O:18])=[CH:15][CH:14]=3)=[N:10][C:9]=2[CH:39]=1)#[N:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 25152049HCID 25152049, compound

Product 1

HCID 25152050HCID 25152050, compoundYield 76.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture was sodium hydride (9 mg, 60% dispersion) in 5 ml of dimethylformamide was added 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-[(5-methyl-2-oxo-1,3-oxazolidin-5-yl)methyl]benzamide (31 mg, EXAMPLE 65) followed by 2-chloro-4-trifluoromethylpyrimidine (14 mg). The mixture was stirred at 70° C. for 1 h. Excess sodium hydride was quenched by addition of 1 ml of methanol. The sample was then purified via mass-directed HPLC on a Kromasil C18 column eluting with a gradient of 10% acetonitrile in water (0.01% TFA) to 60% acetonitrile in water (0.01% TFA) providing the title compound (25 mg, 59%). Mass spectrum (ESI) 565.1 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.94 (d, J=3.9 Hz, 1H), 8.33 (d, J=7.8 Hz, 2H), 7.95 (s, 1H), 7.94 (d, J=7.3 Hz, 2H), 7.52 (s, 1H), 7.36 (d, J=4.1 Hz, 1H), 6.69 (bs, 1H), 4.26 (d, J=11.2 Hz, 1H), 4.12 (d, J=10.7 Hz, 1H), 3.99 (dd, J=14.6, 6.2 Hz, 1H), 3.55 (dd, J=14.8, 6.1 Hz, 1H), 3.48 (sept, J=6.5 Hz, 1H), 1.66 (s, 3H), 1.46 (d, J=6.7 Hz, 6H).

Workup

  1. customExcess sodium hydride was quenched by addition of 1 ml of methanol
  2. customThe sample was then purified via mass-directed HPLC on a Kromasil C18 column
  3. washeluting with a gradient of 10% acetonitrile in water (0.01% TFA) to 60% acetonitrile in water (0.01% TFA)

Sources & evidence

ORD record
ord-44563c6ab9e64fffb53f242ca6f861f9
Source dataset
uspto-grants-2012_10
Patent number
US08293721B2

Reaction notes

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