Dimethylformamide → HCID 178431176, compound

HRID 1492447Notes

Reaction equation

HRID 1492447 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].[NH:17]1[C:21]([C:22]2[CH:23]=[C:24]([NH:28][C:29](=O)[O:30]C3C=CC([N+]([O-])=O)=CC=3)[CH:25]=[CH:26][CH:27]=2)=[N:20][N:19]=[N:18]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:29]([NH:28][C:24]3[CH:25]=[CH:26][CH:27]=[C:22]([C:21]4[NH:17][N:18]=[N:19][N:20]=4)[CH:23]=3)=[O:30])[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 178522026HCID 178522026, compound

Product 1

HCID 178431176HCID 178431176, compoundYield 60%

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, 0.003 mol, from Example 1, part B) and [3-(1H-tetrazol-5-yl)phenylcarbamic acid, 4-nitrophenyl ester (1.08 g, 0.0033 mol, from part A) in acetonitrile (35 mL) and dimethylformamide (20 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 0.5M HCl and water. The organic layer was concentrated in vacuo, and the residue was azeotroped with toluene and triturated with ethyl acetate/hexane (1:1). The product was purified by flash chromatography (EM-60 flash silica gel, 300 mL) and eluted with EtOAc/MeOH/HOAc (20:1:0.06). The solvent was removed in vacuo, acetic acid was azeotroped with toluene and the product was triturated in hexane (40 mL) and ethyl acetate (0.5 mL) and dried in vacuo to give 0.72 g (60%) of the title compound, m.p. 204°-208° C. TLC, silica gel, EtOAc/MeOH/HOAc (20:1:0.2), Rf =0.58; 1H-NMR (DMSO-d6) δ1.3 (s, 3H), 1.5 (s, 3H), 3.7 (d, J=9.4 Hz, 1H), 4.8 (dd, J=8.8 & 8,8 Hz, 1H), 5.8 (s, 1H), 6.8 (d, J=8.2 Hz, 1H), 7.0 (d, J=8.8 Hz, 1H), 7.5 (m, 5H), 8.4 (s, 1H), 9.0 (s, 1H); 13C-NMR (DMSO-d6) δ5 156.6, 156.0. 141.6, 132.9, 132.8, 130.2, 126.2, 125.0, 120.7, 120.1, 119.4, 118.2, 116.5, 103.0, 80.7, 71.6, 49.8, 26.9, 21.4, 19.3; IR (KBr) 2980, 2932, 2228, 1663 cm-1. M.S., (M+H)+ at 406, M.W. 405; [60 ]D=-41.6° (c=0.76 DMSO).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionthe residue, diluted with ethyl acetate
  3. washwas washed with 0.5M HCl and water
  4. concentrationThe organic layer was concentrated in vacuo
  5. customthe residue was azeotroped with toluene
  6. customtriturated with ethyl acetate/hexane (1:1)
  7. customThe product was purified by flash chromatography (EM-60 flash silica gel, 300 mL)
  8. washeluted with EtOAc/MeOH/HOAc (20:1:0.06)
  9. customThe solvent was removed in vacuo, acetic acid
  10. customwas azeotroped with toluene
  11. customthe product was triturated in hexane (40 mL)
  12. dry with materialethyl acetate (0.5 mL) and dried in vacuo

Sources & evidence

ORD record
ord-0e9869a9148a40f7b877d89b4a760e75
Source dataset
uspto-grants-1994_12
Patent number
US05374643

Reaction notes

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