Sodium Carbonate → HCID 86681214, compound

HRID 1848241Notes

Reaction equation

HRID 1848241 reaction equation
Br[C:2]1[CH:28]=[C:27]([F:29])[C:5]2[N:6]([CH2:9][C:10]3[CH:26]=[CH:25][C:13]4[N:14]=[C:15]([NH:17][C@@H:18]5[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]5[OH:24])[S:16][C:12]=4[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1.[CH:30](B1OC(C)(C)C(C)(C)O1)=[CH2:31].C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>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].O>[F:29][C:27]1[C:5]2[N:6]([CH2:9][C:10]3[CH:26]=[CH:25][C:13]4[N:14]=[C:15]([NH:17][C@@H:18]5[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]5[OH:24])[S:16][C:12]=4[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=[C:2]([CH:30]=[CH2:31])[CH:28]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86681211HCID 86681211, compound

Product 1

HCID 86681214HCID 86681214, compoundYield 17.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A stirred mixture of (1R,2R)-2-((6-((5-bromo-7-fluoro-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (150 mg, 0.316 mmol) from Example 203, vinyl boronic acid pinacol ester (97 mg, 0.632 mmol), sodium carbonate (67 mg, 0.0632 mmol), 1,4-dioxane (2 mL), and water (0.5 mL) was purged with a stream of argon. To the mixture was added dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) DCM adduct (35 mg, 0.0474 mmol) and the mixture was heated in a sealed reaction vessel at 100° C. for 2.5 h. The mixture was cooled to rt and purified directly by reverse-phase preparative HPLC using a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase to afford (1R,2R)-2-((6-((7-fluoro-5-vinyl-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (23 mg, 17%) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 8.44 (s, 1H), 7.98 (d, J=7.6 Hz, 1H), 7.55 (d, J=6.9 Hz, 2H), 7.23-7.31 (m, 2H), 7.09 (m, 1H), 6.79 (dd, J=11.0, 17.6 Hz, 1H), 5.83 (d, J=17.5 Hz, 1H), 5.51 (s, 2H), 5.22 (d, J=11.1 Hz, 1H), 4.74 (d, J=4.4 Hz, 1H), 3.51 (br m, 1H), 3.30 (br m, 1H), 2.03 (m, 1H), 1.87 (m, 1H), 1.55-1.67 (m, 2H), 1.14-1.32 (m, 4H); LCMS (ESI) m/z 423 (M+H)+.

Workup

  1. customwas purged with a stream of argon
  2. temperatureThe mixture was cooled to rt
  3. custompurified directly by reverse-phase preparative HPLC
  4. additiona mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase

Sources & evidence

ORD record
ord-28e3c01941d94cd4bff8dcd32806454c
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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