N-cyano-N'-phenylthiourea → HCID 178431174, compound

HRID 847170Notes

Reaction equation

HRID 847170 reaction equation
[C:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=S)#[N:2].[NH2:13][C@@H:14]1[C:19]2[CH:20]=[C:21]([C:24]#[N:25])[CH:22]=[CH:23][C:18]=2[O:17][C:16]([CH3:27])([CH3:26])[C@H:15]1[OH:28].Cl.CN(C)CCCCCN=C=N>CN(C)C=O>[C:1]([N:3]=[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[NH:13][C@@H:14]1[C:19]2[CH:20]=[C:21]([C:24]#[N:25])[CH:22]=[CH:23][C:18]=2[O:17][C:16]([CH3:26])([CH3:27])[C@H:15]1[OH:28])#[N:2]

Participants

5

Reactant 3

HCID 4711553N-cyano-N'-phenylthioureaHCID 10943936(3S,4R)-4-amino-3-hydroxy-2,2-dimethyl-chroman-6-carbonitrileHCID 574828161-(3-Dimethylaminopropyl)-2-ethylcarbodiimide hydrochloride

Product 1

HCID 178431174HCID 178431174, compoundYield 10.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-cyano-N'-phenylthiourea (2.11 g, 11.9 mmol) and (3S-trans)-4-amino-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (2.0 g, 9.1 mmol), title B compound, in dimethylformamide (20 mL) under argon was added 1-(3-dimethylaminopropyl)-2-ethylcarbodiimide hydrochloride (2.23 g, 11.9 mmol) at room temperature. The reaction mixture was stirred at room temperature for 2 hours and then partitioned between 1N hydrochloric acid and ethyl acetate. The organic phase was separated and the aqueous phase was reextracted with ethyl acetate. The combined organic extracts were washed with water, sodium bicarbonate and brine. After drying over anhydrous magnesium sulfate, the solvent was evaporated and the crude product was purified by flash chromatography on silica gel eluting with ethyl acetate/hexanes (7:3) to give a colorless solid which was triturated with ether to yield the title compound (0.35 g), m.p. 215°-216° C.: [α]D25 =-33.5° (c=1, MeOH); 1H NMR (DMSO-d6) δ 9.28 (s, 1 H), 7.58 (d, J=8.0 Hz, 3 H), 7.35 (m, 4 H), 7.15 (m, 1 H), 6.90 (d, J=8.2 Hz, 1 H), 5.92 (br s, 1 H), 4.92 (t, J=9.0 Hz, 1 H), 3.72 (br d, J=5.9 Hz, 1 H), 1.41, 1.18 (s, 3 H each); 13C NMR (DMSO-d6) 159.2, 156.3, 137.5, 132.6, 132.5, 129.0 124.8, 124.7, 123.6, 119.0, 117.8, 117.0, 102.6, 80.4, 70.9, 51.9, 26.6, 18.6; IR (KBr) 2226, 2179, 1609, 1582, 1491, 1267 cm-1.

Workup

  1. custompartitioned between 1N hydrochloric acid and ethyl acetate
  2. customThe organic phase was separated
  3. washThe combined organic extracts were washed with water, sodium bicarbonate and brine
  4. dry with materialAfter drying over anhydrous magnesium sulfate
  5. customthe solvent was evaporated
  6. customthe crude product was purified by flash chromatography on silica gel eluting with ethyl acetate/hexanes (7:3)
  7. customto give a colorless solid which
  8. customwas triturated with ether

Sources & evidence

ORD record
ord-b75d1e5f822744cebc402c99b2411825
Source dataset
uspto-grants-1992_08
Patent number
US05140031

Reaction notes

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