Acetic Acid → HCID 69478876, compound

HRID 1593654Notes

Reaction equation

HRID 1593654 reaction equation
[C:1]([C:5]1[O:9][C:8]([C@@H:10]2[C@H:14]3[O:15][C:16]([CH3:19])([CH3:18])[O:17][C@H:13]3[C@H:12]([N:20]3[CH:28]=[N:27][C:26]4[C:21]3=[N:22][CH:23]=[N:24][C:25]=4Cl)[O:11]2)=[N:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Ca+2].C(O)(=O)C.[Cl:39][C:40]1[CH:46]=[CH:45][C:43]([NH2:44])=[C:42]([F:47])[CH:41]=1>C1(C)C=CC=CC=1>[C:1]([C:5]1[O:9][C:8]([C@@H:10]2[C@H:14]3[O:15][C:16]([CH3:18])([CH3:19])[O:17][C@H:13]3[CH:12]([N:20]3[CH:28]=[N:27][C:26]4[C:21]3=[N:22][CH:23]=[N:24][C:25]=4[NH:44][C:43]3[CH:45]=[CH:46][C:40]([Cl:39])=[CH:41][C:42]=3[F:47])[O:11]2)=[N:7][N:6]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 10112Calcium CarbonateHCID 938984-Chloro-2-fluoroanilineHCID 11316123HCID 11316123, compound

Product 1

HCID 69478876HCID 69478876, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
76 °C

Procedure

To a mixture of 40.0 g (95.1 mmol) of 9-[(3aR,4R,6S,6aS)-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-6-chloro-9H-purine and 9.52 g (95.1 mmol) of CaCO3 powder was successively added 200 mL of glacial acetic acid and 21.1 mL (190 mmol) of 4-chloro-2-fluoroaniline at ambient temperature under nitrogen. The light brown mixture was heated at 76° C. for 1.5 to 2.0 h. The mixture was cooled to below 30° C. and diluted with 200 mL of toluene. The mixture was concentrated to about 120 mL by distillation at 35-45° C. under vacuum below 50 torr. This azeotropic process was repeated with a second charge of 240 mL of toluene and distilled to about 200 mL. The above mixture was filtered by suction and the filtrate was concentrated to about 80 mL at 35-45° C. under vacuum to provide a toluene solution of crude product of N-{9-[(3aR,6S,6aS)-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-2,2-dimethyltetrahydrofuro [3,4-d][1,3]dioxol-4-yl]-9H-purin-6-yl}N-(4-chloro-2-fluorophenyl)amine.

Workup

  1. customat ambient temperature
  2. temperatureThe mixture was cooled to below 30° C.
  3. concentrationThe mixture was concentrated to about 120 mL by distillation at 35-45° C. under vacuum below 50 torr
  4. additiona second charge of 240 mL of toluene
  5. distillationdistilled to about 200 mL
  6. filtrationThe above mixture was filtered by suction
  7. concentrationthe filtrate was concentrated to about 80 mL at 35-45° C. under vacuum

Sources & evidence

ORD record
ord-2b280b45e08c49dcbf4350a914cdb01c
Source dataset
uspto-grants-2007_11
Patent number
US07297787B2

Reaction notes

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