Potassium Carbonate → HCID 68283746, compound

HRID 1855302Notes

Reaction equation

HRID 1855302 reaction equation
C(=O)([O-])[O-].[K+].[K+].[F:7][C:8]1[CH:13]=[C:12](B(O)O)[CH:11]=[CH:10][N:9]=1.FC(F)(F)S(O[C:23]1[CH:36]=[C:35]2[C:26]([O:27][C:28]3[CH:29]=[CH:30][C:31]([C:52]4[C:53]([F:58])=[N:54][CH:55]=[CH:56][CH:57]=4)=[CH:32][C:33]=3[C:34]32[C:40]2=[N:41][CH:42]=[CH:43][N:39]2[C:38]([NH:44][C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])=[N:37]3)=[C:25]([F:59])[CH:24]=1)(=O)=O>O1CCOCC1.O>[F:59][C:25]1[C:26]2[O:27][C:28]3[C:33](=[CH:32][C:31]([C:52]4[C:53]([F:58])=[N:54][CH:55]=[CH:56][CH:57]=4)=[CH:30][CH:29]=3)[C:34]3([C:40]4=[N:41][CH:42]=[CH:43][N:39]4[C:38]([NH:44][C:45](=[O:46])[O:47][C:48]([CH3:50])([CH3:49])[CH3:51])=[N:37]3)[C:35]=2[CH:36]=[C:23]([C:12]2[CH:11]=[CH:10][N:9]=[C:8]([F:7])[CH:13]=2)[CH:24]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27833962-Fluoropyridine-4-boronic acidHCID 86710010HCID 86710010, compound

Product 1

HCID 68283746HCID 68283746, compoundYield 54.5%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

PdCl2dppf (25.1 mg, 0.031 mmol), potassium carbonate (1232 μL, 1.232 mmol), 2-fluoropyridin-4-ylboronic acid (87 mg, 0.616 mmol), and 5-(tert-butoxycarbonylamino)-5′-fluoro-2′-(2-fluoropyridin-3-yl)spiro[imidazo[1,5-a]imidazole-7,9′-xanthene]-7′-yl trifluoromethanesulfonate (200 mg, 0.308 mmol) were combined in dioxane/water 4:1 (3079 μL) and heated at 100° C. for 2 hours. The solution was concentrated. The product was purified via silica gel column chromatography using 0-60% EtOAc in hexane to afford tert-butyl 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-(2-fluoropyridin-4-yl)spiro[imidazo[1,5-a]imidazole-7,9′-xanthene]-5-ylcarbamate (100 mg, 0.168 mmol, 54.4% yield). This material was treated with TFA (0.323 ml, 4.19 mmol) in DCM (2 ml) and stirred at RT for 1 hr. The solution was concentrated, and the racemic residue was separated by SFC using an IC (10×0.46 cm) column, eluting with 20% IPA (DEA)/CO2, 100 bar, 4 mL/min, 220 nm to afford (S)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-(2-fluoropyridin-4-yl)spiro[imidazo[1,5-a]imidazole-7,9′-xanthen]-5-amine (Example 8A) and (R)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-(2-fluoropyridin-4-yl)spiro[imidazo[1,5-a]imidazole-7,9′-xanthen]-5-amine (Example 8B). Mass Spec is in Table 1.

Workup

  1. concentrationThe solution was concentrated
  2. customThe product was purified via silica gel column chromatography

Sources & evidence

ORD record
ord-a30fdb3f32284898bbb553b06b009504
Source dataset
uspto-grants-2015_02
Patent number
US08962859B2

Reaction notes

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