Hydrochloric Acid → 4-[(3R)-3-{[6-(2-Fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidin-4-yl]oxy}piperidin-1-yl]butyric acid methyl ester

HRID 2189124Notes

Reaction equation

HRID 2189124 reaction equation
C(=O)([O-])[O-].[K+].[K+].[F:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[O:29][C:17]2[N:18]=[CH:19][N:20]=[C:21]([O:22][C@@H:23]3[CH2:28][CH2:27][CH2:26][NH:25][CH2:24]3)[C:16]=2[C:15]=1[C:30]1[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=1.[CH3:38][O:39][C:40](=[O:45])[CH2:41][CH2:42][CH2:43]Br.Cl>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C.O.CN(C=O)C>[CH3:38][O:39][C:40](=[O:45])[CH2:41][CH2:42][CH2:43][N:25]1[CH2:26][CH2:27][CH2:28][C@@H:23]([O:22][C:21]2[C:16]3[C:15]([C:30]4[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=4)=[C:14]([C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=4[F:7])[O:29][C:17]=3[N:18]=[CH:19][N:20]=2)[CH2:24]1

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 107604Methyl 4-bromobutyrateHCID 671600016-(2-Fluorophenyl)-5-(4-methoxyphenyl)-4-[(3R)-piperidin-3-yloxy]furo[2,3-d]pyrimidine

Product 1

HCID 582800764-[(3R)-3-{[6-(2-Fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidin-4-yl]oxy}piperidin-1-yl]butyric acid methyl ester

Reagents, catalysts & solvents 5

HCID 67553Tetrabutylammonium IodideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

411 mg (3.0 mmol) of potassium carbonate are added to a suspension of 500 mg (1.2 mmol) of 6-(2-fluorophenyl)-5-(4-methoxyphenyl)-4-[(3R)-piperidin-3-yloxy]furo[2,3-d]pyrimidine in 10 ml of THF. Then add 0.18 ml (259 mg, 1.4 mmol) of 4-bromobutyric acid methyl ester and 17 mg (0.05 mmol) of tetra-n-butylammonium iodide. Stir the reaction mixture at 80° C. for 13 hours. Then add 10 ml of DMF and again stir the mixture at 70° C. for 13 hours. After adding 10 ml each of water, 1N hydrochloric acid and ethyl acetate, remove the organic phase, concentrate under reduced pressure and purify the residue by means of preparative RP-HPLC eluent: water/acetonitrile gradient). 146 mg (22% of theory) of the target compound are obtained.

Workup

  1. stirringagain stir the mixture at 70° C. for 13 hours
  2. customremove the organic phase
  3. concentrationconcentrate under reduced pressure
  4. custompurify the residue by means of preparative RP-HPLC eluent
  5. custom146 mg (22% of theory) of the target compound are obtained

Sources & evidence

ORD record
ord-07d00d73f558442fa033cb7ff82ade17
Source dataset
uspto-grants-2012_12
Patent number
US08324222B2

Reaction notes

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