Dimethylformamide → HCID 57297137, compound

HRID 1492452Notes

Reaction equation

HRID 1492452 reaction equation
N[C@@H]1[C:7]2[CH:8]=[C:9]([C:12]#[N:13])[CH:10]=[CH:11][C:6]=2OC(C)(C)[C@H]1O.[C:17]([C:19]1[CH:20]=[CH:21][C:22]2[O:27][C:26]([CH3:29])([CH3:28])[C@@H:25]([OH:30])[C@H:24]([N:31](C3C=C4C(=CC=3)CCC4)[C:32](=[O:34])[NH2:33])[C:23]=2[CH:44]=1)#[N:18].CN(C)C=[O:48].[C:50](#[N:52])C>>[C:17]([C:19]1[CH:20]=[CH:21][C:22]2[O:27][C:26]([CH3:28])([CH3:29])[C@@H:25]([OH:30])[C@H:24]([NH:31][C:32]([NH:33][C:6]3[CH:7]=[CH:8][C:9]([C:12]4[O:48][N:52]=[CH:50][N:13]=4)=[CH:10][CH:11]=3)=[O:34])[C:23]=2[CH:44]=1)#[N:18]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 6342AcetonitrileHCID 10943936(3S,4R)-4-amino-3-hydroxy-2,2-dimethyl-chroman-6-carbonitrileHCID 67848883HCID 67848883, compound

Product 1

HCID 57297137HCID 57297137, compoundYield 70%

Procedure

A mixture of (3S-trans)-4-amino-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (0.65 g, 0.0030 mol, compound of Example 1, part B) and the compound of title B (1.37 g, 0.0042 mol) in acetonitrile (20 mL) and dimethylformamide (30 mL) was heated 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 hexanes/EtOAc (2:1) and hexanes/EtOAc (1:1). The solvent was removed in vacuo, to give a solid that was triturated with anhydrous ether and dried in vacuo to yield 0.75 g (70%) of the title compound, m.p. 162°-167° C. TLC, silica gel, EtOAc/hexanes (2:1), Rf =0.34. 1H-NMR (DMSO-d6) δ9.2 (s, 1H), 9.0 (s, 1H), 8.0 (d, J=8.8 Hz, 2H), 7.7 (d, J=8.8 Hz, 2H), 7.6 (m, 2H), 7.0 (d, J=9.4 Hz, 1H), 5 6.8 (d, J=8.8 Hz, 1H), 5.7 (s, 1H), 4.7 (t, J=8.8 Hz, 1H), 3.7 (dd, J=5.9 & 3.5 Hz, 1H), 1.4 (s, 3H), 1.2 (s, 3H); 13C-NMR (DMSO-d6) δ174.6, 158.4, 156.3, 155.4, 145.0, 132.6, 129.0, 125.7, 119.1, 117.9, 117.8, 115.7, 102.7, 80.4, 71.3, 49.5, 26.5, 18.9; IR (KBr) 2226, 1672, 1603, 1539, 1462 cm-1M.S. (M+H)+ at 406, M.W. 405; [α]D =-76.2° (c=0.86 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 hexanes/EtOAc (2:1) and hexanes/EtOAc (1:1)
  8. customThe solvent was removed in vacuo
  9. customto give a solid
  10. customthat was triturated with anhydrous ether
  11. customdried in vacuo

Sources & evidence

ORD record
ord-380482a94bbf495e9a422f2ac5a25222
Source dataset
uspto-grants-1994_12
Patent number
US05374643

Reaction notes

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