Trifluoroacetic acid → 10-(5-Chlorofuran-2-yl)-8-((1,3-dioxoisoindolin-2-yl)methyl)-1,3-dimethyl-5-(4-methylthiazol-2-yl)-7,8-dihydro-1H-pyrimido[4',5':3,4]pyrrolo[2,1-c][1,4]thiazine-2,4(3H,10H)-dione

HRID 2201230Notes

Reaction equation

HRID 2201230 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=O.[O:8]=[C:9]1[C:17]2C(=[CH:13][CH:14]=[CH:15][CH:16]=2)C(=O)[N:10]1[CH2:19][CH:20]([S:41]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:21][N:22]1[C:30]([C:31]2[S:32][CH:33]=[C:34]([CH3:36])[N:35]=2)=[C:29]2[C:24]([N:25]([CH3:40])[C:26](=[O:39])[N:27]([CH3:38])[C:28]2=[O:37])=[CH:23]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.[Cl:86][C:87]1[O:91][C:90]([CH:92]=O)=[CH:89][CH:88]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:86][C:87]1[O:91][C:90]([CH:92]2[C:23]3=[C:24]4[N:25]([CH3:40])[C:26](=[O:39])[N:27]([CH3:38])[C:28](=[O:37])[C:29]4=[C:30]([C:31]4[S:32][CH:33]=[C:34]([CH3:36])[N:35]=4)[N:22]3[CH2:21][CH:20]([CH2:19][N:10]3[C:3](=[O:5])[C:2]4[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=4)[C:9]3=[O:8])[S:41]2)=[CH:89][CH:88]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 27696305-Chloro-2-furaldehydeHCID 9917655Bi(OTf)3HCID 867234646-(3-(1,3-Dioxoisoindolin-2-yl)-2-(tritylthio)propyl)-1,3-dimethyl-5-(4-methylthiazol-2-yl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

Product 1

HCID 8672346610-(5-Chlorofuran-2-yl)-8-((1,3-dioxoisoindolin-2-yl)methyl)-1,3-dimethyl-5-(4-methylthiazol-2-yl)-7,8-dihydro-1H-pyrimido[4',5':3,4]pyrrolo[2,1-c][1,4]thiazine-2,4(3H,10H)-dione

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Trifluoroacetic acid (0.399 ml, 5.18 mmol) was added to a solution of 6-(3-(1,3-dioxoisoindolin-2-yl)-2-(tritylthio)propyl)-1,3-dimethyl-5-(4-methylthiazol-2-yl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (764 mg, 1.035 mmol) in toluene (15 ml) and the mixture was stirred at room temperature for 30 minutes. Bismuth triflate (340 mg, 0.518 mmol) and 5-chlorofuran-2-carbaldehyde (203 mg, 1.553 mmol) were then added and the mixture was stirred at room temperature for 16 hours. The mixture was then diluted with ethyl acetate (150 ml) and washed with water (150 ml), saturated NaHCO3(aq) (150 ml) and brine (150 ml). The organic layer was dried over magnesium sulfate and evaporated under vacuum. Purification by chromatography on silica, eluting with 0-100% EtOAc/hexane, afforded the title compound as a mixture of diastereomers.

Workup

  1. stirringthe mixture was stirred at room temperature for 16 hours
  2. washwashed with water (150 ml), saturated NaHCO3(aq) (150 ml) and brine (150 ml)
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. customevaporated under vacuum
  5. customPurification by chromatography on silica
  6. washeluting with 0-100% EtOAc/hexane

Sources & evidence

ORD record
ord-421965f643b24297ad79b0e2c96cce48
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Reaction notes

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