Tetrahydrofuran → HCID 71257245, compound

HRID 710182Notes

Reaction equation

HRID 710182 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[C:12]1[O:13][C:14]2[CH:20]=[CH:19][C:18]([C:21]3[CH2:26][CH2:25][N:24]([S:27]([CH2:30][C:31](OCC)=O)(=[O:29])=[O:28])[CH2:23][CH:22]=3)=[CH:17][C:15]=2[N:16]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C1C[O:45][CH2:44]C1>>[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[C:12]1[O:13][C:14]2[CH:20]=[CH:19][C:18]([C:21]3[CH2:26][CH2:25][N:24]([S:27]([CH2:30][CH2:31][CH2:44][OH:45])(=[O:28])=[O:29])[CH2:23][CH:22]=3)=[CH:17][C:15]=2[N:16]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 21226445Aluminium lithium hydrideHCID 71257247HCID 71257247, compound

Product 1

HCID 71257245HCID 71257245, compound

Procedure

Example 59 (200 mg, 0.42 mmol) was dissolved in DCM (30 ml) and added TFA (1.5 ml, 9.2 mmol). This mixture was stirred at rt for 3 h and DCM was removed on rotavapour to obtain a residue. Residue was co-distilled with diethyl ether to obtain 2-(2-fluoro-4-(methyl sulfonyl)phenyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (210 mg). 2-(2-fluoro-4-(methylsulfonyl)phenyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (200 mg, 0.4 mmol) was dissolved in DCM (10 ml) and added TEA (0.46 ml, 3.3 mmol). This mixture was stirred at rt for 30 mins. After 30 mins reaction mixture cooled to 0° C. and added ethyl 3-(chlorosulfonyl)propanoate (164 mg, 0.4 mmol). This reaction continued for 30 mins at rt. Work up (H2O/DCM) followed by column purification on combiflash using a gradient mixture of EtOAc and Petether (45:55) as eluent afforded ethyl 2-{4-[2-(2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-5-yl}-5,6-dihydropyridin-1(2H)-ylsulfonyl)acetate (120 mg). Ethyl 2-{4-[2-(2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-5-yl}-5,6-dihydropyridin-1(2H)-ylsulfonyl)acetate (100 mg, 0.19 mmol) was dissolved in THF (5 ml) and added Lithiumaluminium hydride (14 mg, 0.38 mmol) at 0° C. This mixture was stirred at same temperature for 90 mins. After completion of the reaction, reaction mass quenched with 1N HCl (7 ml). Work up (DCM/H2O) followed by purification on combiflash using a gradient mixture of EtOAc and Petether (80:20) as eluent afforded the titled compound (40 mg) as a white solid. M.P.: 184-186° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 8.48 (t, J 8.1, 1H), 8.06 (dd, J 1.6, 10.1, 1H), 8.00-7.94 (m, 2H), 7.84 (d, J 8.6, 1H), 7.63 (dd, J 1.8, 8.5, 1H), 6.29 (s, 1H), 4.64 (t, J 5.3, 1H), 3.94 (d, J 2.9, 2H), 3.50-3.42 (m, 4H), 3.36 (s, 3H), 3.18-3.10 (m, 2H), 2.70-2.62 (m, 2H), 1.88-1.80 (m, 2H).

Workup

  1. customAfter completion of the reaction, reaction mass
  2. customquenched with 1N HCl (7 ml)
  3. customfollowed by purification on combiflash
  4. additiona gradient mixture of EtOAc and Petether (80:20) as eluent

Sources & evidence

ORD record
ord-d7ce7bad4b4c4e29be9713c368213287
Source dataset
uspto-grants-2015_11
Patent number
US09181214B2

Reaction notes

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