Dimethylformamide → (3S-trans)-N-(6-Cyano-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl)-N'-[3-[3-methyl-(1,2,4-oxadiazol-5-yl)]phenyl]urea

HRID 1492454Notes

Reaction equation

HRID 1492454 reaction equation
[NH2:1][C@@H:2]1[C:7]2[CH:8]=[C:9]([C:12]#[N:13])[CH:10]=[CH:11][C:6]=2[O:5][C:4]([CH3:15])([CH3:14])[C@H:3]1[OH:16].[CH3:17][C:18]1[N:22]=[C:21]([C:23]2[CH:24]=[C:25]([NH:29][C:30](=O)[O:31]C3C=CC([N+]([O-])=O)=CC=3)[CH:26]=[CH:27][CH:28]=2)[O:20][N:19]=1.CN(C)C=O>C(#N)C>[C:12]([C:9]1[CH:10]=[CH:11][C:6]2[O:5][C:4]([CH3:14])([CH3:15])[C@@H:3]([OH:16])[C@H:2]([NH:1][C:30]([NH:29][C:25]3[CH:26]=[CH:27][CH:28]=[C:23]([C:21]4[O:20][N:19]=[C:18]([CH3:17])[N:22]=4)[CH:24]=3)=[O:31])[C:7]=2[CH:8]=1)#[N:13]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 10943936(3S,4R)-4-amino-3-hydroxy-2,2-dimethyl-chroman-6-carbonitrileHCID 57105596[3-[3-Methyl(1,2,4-oxadiazol-5-yl)]phenyl]carbamic acid, 4-nitrophenyl ester

Product 1

HCID 18657724(3S-trans)-N-(6-Cyano-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl)-N'-[3-[3-methyl-(1,2,4-oxadiazol-5-yl)]phenyl]urea

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of (3S-trans)-4-amino-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (0.65 g, 3.0 mmol, from Example 1, part B) and [3-[3-methyl(1,2,4-oxadiazol-5-yl)]phenyl]carbamic acid, 4-nitrophenyl ester (1.12 g, 3.3 mmol, title A compound) in acetonitrile (20 mL) and dimethyl-formamide (40 mL) was stirred at 80° C. for two hours. The reaction mixture was concentrated in vacuo and the residue, diluted with ethyl acetate, was washed with 10% citric acid and water. The organic layer was dried over MgSO4 and concentrated in vacuo. The product was purified by flash chromatography (Sorbisol C 60 flash silica gel, 400 mL) and eluted with Hexane/EtOAc (1:1). The solvent was removed in vacuo, to give a solid that was triturated in hexane and dried in vacuo to yield 1.10 g of the title compound, m.p. 157°-161 ° C. TLC, silica gel, EtOAc/Hexane(2:1), Rf =0.41. 1H-NMR (DMSO-d6) δ9.1 (s, 1H), 8.4 (s, 1H), 7.5 (m, 5H), 6.9 (d, J=9.4 Hz, 1H), 6.8 (d, J=8.2 Hz, 1H), 5.7 (d, J=5.9 Hz, 1H), 4.7 (t, J=8.8 Hz, 1H), 3.7 (dd, J =5.9 & 4.1Hz, 1H), 2.4 (s, 3H), 1.4 (s, 3H), 1.2 (s, 3H); 13C-NMR (DMSO-d6) δ174.9, 167.6, 156.3, 155.6, 141.4, 132.6, 132.5, 130.0, 125.9, 123.8, 122.1, 120.4, 119.1, 117.9. 116.6, 102.76, 80.4, 71.2, 49.5, 26.5, 18.9, 11.3; IR (KBr) 2980, 2228, 1670, 1574, 1553, 1489 cm-1. M.S. (M+H)+ at 420, M.W. 419; [α]D =-43.6° (c=0.77 DMSO).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionthe residue, diluted with ethyl acetate
  3. washwas washed with 10% citric acid and water
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe product was purified by flash chromatography (Sorbisol C 60 flash silica gel, 400 mL)
  7. washeluted with Hexane/EtOAc (1:1)
  8. customThe solvent was removed in vacuo
  9. customto give a solid
  10. customthat was triturated in hexane
  11. customdried in vacuo

Sources & evidence

ORD record
ord-c5e59206bd5a4a67b3050523185e8a7d
Source dataset
uspto-grants-1994_12
Patent number
US05374643

Reaction notes

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