Diethyl Ether → 3-(10-(5-Chlorofuran-2-yl)-1,3-dimethyl-2,4-dioxo-2,3,4,7,8,10-hexahydro-1H-pyrimido[4',5':3,4]pyrrolo[2,1-c][1,4]thiazin-5-yl)benzonitrile

HRID 2201172

Reaction equation

HRID 2201172 reaction equation
[SH:1][CH2:2][CH2:3][N:4]1[C:12]([C:13]2[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=2)[C:16]#[N:17])=[C:11]2[C:6]([N:7]([CH3:24])[C:8](=[O:23])[N:9]([CH3:22])[C:10]2=[O:21])=[CH:5]1.[Cl:25][C:26]1[O:30][C:29]([CH:31]=O)=[CH:28][CH:27]=1.[O-]S(C(F)(F)F)(=O)=O.[Bi+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O.C(OCC)C>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:25][C:26]1[O:30][C:29]([CH:31]2[C:5]3=[C:6]4[N:7]([CH3:24])[C:8](=[O:23])[N:9]([CH3:22])[C:10](=[O:21])[C:11]4=[C:12]([C:13]4[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=4)[C:16]#[N:17])[N:4]3[CH2:3][CH2:2][S:1]2)=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 27696305-Chloro-2-furaldehydeHCID 9917655Bi(OTf)3HCID 867234173-(6-(2-mercaptoethyl)-1,3-dimethyl-2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-5-yl)benzonitrile2×

Product 1

HCID 771054153-(10-(5-Chlorofuran-2-yl)-1,3-dimethyl-2,4-dioxo-2,3,4,7,8,10-hexahydro-1H-pyrimido[4',5':3,4]pyrrolo[2,1-c][1,4]thiazin-5-yl)benzonitrile

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A suspension comprising 3-(6-(2-mercaptoethyl)-1,3-dimethyl-2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-5-yl)benzonitrile (Intermediate G) (150 mg, 0.441 mmol), 5-chlorofuran-2-carbaldehyde (57.5 mg, 0.441 mmol) and bismuth triflate (28.9 mg, 0.044 mmol) in toluene (5 ml) was heated to 100° C. for 10 min using microwave radiation. After cooling to RT, the reaction mixture was diluted with EtOAc (25 ml) and washed with water. The layers were separated and the aqueous extracted with EtOAc (3×20 ml). The combined organics were dried over MgSO4, filtered and concentrated to yield a brown oil. Purification was carried out by chromatography on silica eluting with 0-45% EtOAc in iso-hexane. The relevant fraction were combined and concentrated in vacuo to yield a pale yellow oil. Diethyl ether (5 ml) was added to the oil to give a white solid. The solid was isolated by suction filtration to afford the title compound.

Workup

  1. temperatureAfter cooling to RT
  2. washwashed with water
  3. customThe layers were separated
  4. extractionthe aqueous extracted with EtOAc (3×20 ml)
  5. dry with materialThe combined organics were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a brown oil
  9. customPurification
  10. concentrationconcentrated in vacuo
  11. customto yield a pale yellow oil
  12. customto give a white solid
  13. customThe solid was isolated by suction filtration

Sources & evidence

ORD record
ord-c6e3b904576a4b49a69f45abdbcb2c68
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Linked notes

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