Sodium Carbonate → 4-{[(3R)-1-Benzylpiperidin-3-yl]oxy}-5-(4-ethylphenyl)-6-(2-fluorophenyl)furo[2,3-d]pyrimidine

HRID 2189073Notes

Reaction equation

C(=O)([O-])[O-].[Na+].[Na+].[CH2:7]([N:14]1[CH2:19][CH2:18][CH2:17][C@@H:16]([O:20][C:21]2[C:22]3[C:29]([C:30]4[CH:35]=[CH:34][C:33]([CH2:36][CH3:37])=[CH:32][CH:31]=4)=[C:28](I)[O:27][C:23]=3[N:24]=[CH:25][N:26]=2)[CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[F:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1B(O)O>CS(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:7]([N:14]1[CH2:19][CH2:18][CH2:17][C@@H:16]([O:20][C:21]2[C:22]3[C:29]([C:30]4[CH:35]=[CH:34][C:33]([CH2:36][CH3:37])=[CH:32][CH:31]=4)=[C:28]([C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=4[F:39])[O:27][C:23]=3[N:24]=[CH:25][N:26]=2)[CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Add 0.68 ml of a 2 M aqueous sodium carbonate solution to a mixture of 365 mg (0.68 mmol) of 4-{[(3R)-1-benzylpiperidin-3-yl]oxy}-5-(4-ethylphenyl)-6-iodofuro[2,3-d]pyrimidine and 24 mg (0.03 mmol) of bis(triphenylphosphine)palladium(II) chloride in 15 ml of DMSO. Then add 118 mg (0.85 mmol) of (2-fluorophenyl)boronic acid and stir the mixture at 80° C. for 15 hours. Then filter the reaction mixture and purify directly by means of preparative RP-HPLC (gradient: water/acetonitrile). 291 mg (84% of theory) of the target compound are obtained.

Workup

filtrationThen filter the reaction mixture
custompurify directly by means of preparative RP-HPLC (gradient: water/acetonitrile)
custom291 mg (84% of theory) of the target compound are obtained

Sources & evidence

ORD record: ord-e9ff6daedb824b5a892bdb98ce30d768
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08324222B2

Reaction notes

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