Phenyl isocyanate → (trans)-1-(6-Cyano-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-phenylurea

HRID 1197685Notes

Reaction equation

HRID 1197685 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].[C:17]1([N:23]=[C:24]=[O:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(O)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:24]([NH:23][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:25])[C:7]=2[CH:8]=1)#[N:13]

Participants

4

Reactant 2

HCID 7672Phenyl isocyanateHCID 10943936(3S,4R)-4-amino-3-hydroxy-2,2-dimethyl-chroman-6-carbonitrile

Product 1

HCID 9905823(trans)-1-(6-Cyano-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl)-3-phenylureaYield 63%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A suspension of (trans)-4-amino-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (prepared according to Evans et al., J. Med. Chem., 1983, 26, p. 1582 and J. Med. Chem., 1986, 29, p. 2194) (1.0 g, 4.6 mmol) in ethanol (4 ml) under argon was treated with phenylisocyanate (0.55 g, 4.6 mmol) and the reaction was heated at reflux temperature for 4 hours. The product precipitate out of the reaction. The reaction was then concentrated in vacuo and the residue was triturated with isopropylether to give the title compound as a colorless solid (0.9 g, 63%), m.p. 240-241° C.: 1H NMR (CDCl3 /DMSO) δ 8.3 (s, 1 H), 7.7 (s, 1 H), 7.4 (d, J=8.0 Hz, 3 H), 7.26 (t, J=8.0 Hz, 2 H), 7.0 (t, J=9.0 & 7.0 Hz, 1 H), 6.86 (d, J=9.0 Hz, 1 H), 6.4 (d, J=8.0 Hz, 1 H), 5.3 (d, J=5.0 Hz, 1 H), 4.9 (t, J=9.0 & 8.0 Hz, 1 H), 3.6 (dd, J=4.0 & 6.0 Hz, 1 H), 1.5 (s, 3 H), 1.3 (s, 3 H); 13C NMR (CDCl3 /DMSO) 157.0, 156.5, 139.1, 132.2, 132.1, 128.4, 123.9, 121.8, 118.2, 117.8, 80.0, 74.3, 49.9, 26.1, 18.4; IR (KBr) 1132, 1267, 1491, 1550, 1612, 1645, 2226, 2932, 2978, 3433 cm-1.

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux temperature for 4 hours
  3. customThe product precipitate out of the reaction
  4. concentrationThe reaction was then concentrated in vacuo
  5. customthe residue was triturated with isopropylether

Sources & evidence

ORD record
ord-d7b91eb190564841b7c71533f6f6fd27
Source dataset
uspto-grants-1994_01
Patent number
US05276168

Reaction notes

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