Hydrochloric Acid → 5-Fluoro-3-phenyl-2-{(S)-1-[9-(tetrahydropyran-2-yl)-9H-purin-6-ylamino]ethyl}-3H-benzoimidazole-4-carboxylic acid

HRID 242980Notes

Reaction equation

HRID 242980 reaction equation
C[O:2][C:3]([C:5]1[C:13]2[N:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:11]([C@@H:20]([NH:22][C:23]3[N:31]=[CH:30][N:29]=[C:28]4[C:24]=3[N:25]=[CH:26][N:27]4[CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][O:33]3)[CH3:21])=[N:10][C:9]=2[CH:8]=[CH:7][C:6]=1[F:38])=[O:4].O[Li].O.Cl>CO.O>[F:38][C:6]1[CH:7]=[CH:8][C:9]2[N:10]=[C:11]([C@@H:20]([NH:22][C:23]3[N:31]=[CH:30][N:29]=[C:28]4[C:24]=3[N:25]=[CH:26][N:27]4[CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][O:33]3)[CH3:21])[N:12]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:13]=2[C:5]=1[C:3]([OH:4])=[O:2]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrate3×HCID 68157522HCID 68157522, compound

Product 1

HCID 681574615-Fluoro-3-phenyl-2-{(S)-1-[9-(tetrahydropyran-2-yl)-9H-purin-6-ylamino]ethyl}-3H-benzoimidazole-4-carboxylic acidYield 73%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 5-fluoro-3-phenyl-2-{(S)-1-[9-(tetrahydropyran-2-yl)-9H-purin-6-ylamino]ethyl}-3H-benzoimidazole-4-carboxylic acid methyl ester (580 mg, 1.13 mmol) and LiOH.H2O (94 mg, 2.25 mmol) in MeOH (20 mL) and water (2 mL) was heated at 45° C. for 3 h. Additional LiOH.H2O (94 mg) was added and the mixture heated at 80° C. for 16 h. After further addition of LiOH.H2O (94 mg), stirring at 75° C. was continued for 18 h. After cooling to RT, the pH of the mixture was adjusted to 4 by addition of 1N HCl. The organic solvent was removed under reduced pressure and EtOAc was added to the crude mixture. After sonication of the suspension, the organic solvent was removed in vacuo. The solid was collected by filtration and dried in vacuo to afford the title compound (412 mg, 73%). LCMS (Method C): RT 2.40 min [M+H]+ 502.0.

Workup

  1. temperatureAfter cooling to RT
  2. customThe organic solvent was removed under reduced pressure and EtOAc
  3. additionwas added to the crude mixture
  4. customAfter sonication of the suspension
  5. customthe organic solvent was removed in vacuo
  6. filtrationThe solid was collected by filtration
  7. customdried in vacuo

Sources & evidence

ORD record
ord-af986b267f1049f6a5ffc00590cbc291
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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