Potassium Carbonate → HCID 71543161, compound

HRID 931657Notes

Reaction equation

HRID 931657 reaction equation
FC(F)(F)S(O[C:7]1[CH:20]=[C:19]2[C:10]([O:11][C:12]3[CH:13]=[CH:14][C:15]([NH:27][C:28]([C:30]4[CH:35]=[N:34][C:33]([O:36][CH3:37])=[CH:32][N:31]=4)=[O:29])=[CH:16][C:17]=3[C@:18]32[CH2:25][CH2:24][S:23][C:22]([NH2:26])=[N:21]3)=[C:9]([F:38])[CH:8]=1)(=O)=O.[O:41]1[CH2:46][CH:45]=[C:44](B2OC(C)(C)C(C)(C)O2)[CH2:43][CH2:42]1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[NH2:26][C:22]1[S:23][CH2:24][CH2:25][C@:18]2([N:21]=1)[C:17]1[CH:16]=[C:15]([NH:27][C:28]([C:30]3[CH:35]=[N:34][C:33]([O:36][CH3:37])=[CH:32][N:31]=3)=[O:29])[CH:14]=[CH:13][C:12]=1[O:11][C:10]1[C:19]2=[CH:20][C:7]([C:44]2[CH2:45][CH2:46][O:41][CH2:42][CH:43]=2)=[CH:8][C:9]=1[F:38]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 117600049HCID 117600049, compound

Product 1

HCID 71543161HCID 71543161, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

To a microwave vial were charged with (S)-2-amino-5′-fluoro-2′-(5-methoxypyrazine-2-carboxamido)-5,6-dihydrospiro[[1,3]thiazine-4,9′-xanthen]-7′-yl trifluoromethanesulfonate (0.050 g, 0.083 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.039 g, 0.183 mmol), and PdCl2(dppf)2 (10.22 mg, 0.013 mmol). After purged with N2 for 5 min, potassium carbonate (1.5M in water) (0.167 ml, 0.250 mmol) and Dioxane (0.75 ml) were added. The reaction mixture was microwaved at 110° C. for 10 mins. LCMS indicated complete conversion to the desired product. The reaction mixture was partitioned between EtOAc and water. The organic layer was concentrated and then purified by Shimadzu HPLC to afford 50 mg of (S)—N-(2-amino-2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-5,6-dihydrospiro[[1,3]thiazine-4,9′-xanthen]-7′-yl)-5-methoxypyrazine-2-carboxamide as off-white solid (TFA salt). MS m/z=534.2 [M+H].

Workup

  1. customAfter purged with N2 for 5 min
  2. customThe reaction mixture was microwaved at 110° C. for 10 mins

Sources & evidence

ORD record
ord-5b62b60c84624cd78c2611edfb1061c5
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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