Potassium Carbonate → HCID 71550000, compound

HRID 1848021Notes

Reaction equation

HRID 1848021 reaction equation
Br[C:2]1[C:28]([O:29][CH3:30])=[CH:27][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.[CH3:31][N:32]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[N:33]1.C([O-])([O-])=O.[K+].[K+]>COCCOC.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>[CH3:30][O:29][C:28]1[C:2]([C:35]2[CH:34]=[N:33][N:32]([CH3:31])[CH:36]=2)=[CH:3][C:4]2[N:8]=[CH:7][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)[C:5]=2[CH:27]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 71550134HCID 71550134, compound

Product 1

HCID 71550000HCID 71550000, compoundYield 54.6%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A suspension of (1R,2R)-2-((6-((5-bromo-6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (30 mg, 0.06 mmol) from Step 1 of this Example and 1-methylpyrazole-4-boronic acid pinacol ester (26 mg, 0.1 mmol) in DME (300 μL) was added aq 2M K2CO3 (150 μL, 0.2 mmol). Argon was bubbled into the mixture for 5 min followed by the addition of dichlorobis(triphenylphosphine)palladium II (4 mg, 0.006 mmol). Argon was bubbled into the mixture for an additional 5 min and then the mixture was heated in a sealed tube for 15 h. The mixture was cooled to rt and then partitioned between EtOAc (100 mL) and water (50 mL). The EtOAc layer was separated and concentrated under reduced pressure. The residue was purified by reverse-phase preparative HPLC, using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase to afford (1R,2R)-2-((6-((6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (16 mg, 53%) as a white powder. 1H NMR (300 MHz, DMSO-d6) δ 8.21 (s, 1H), 7.97-8.06 (m, 2H), 7.87 (s, 1H), 7.80 (s, 1H), 7.66 (d, J=1.1 Hz, 1H), 7.27-7.33 (m, 1H), 7.19-7.25 (m, 2H), 5.44 (s, 2H), 4.78 (d, J=4.3 Hz, 1H), 3.85 (s, 6H), 3.51 (m, 1H), 3.33 (m, 1H), 2.03 (m, 1H), 1.87 (m, 1H), 1.56-1.66 (m, 2H), 1.12-1.32 (m, 4H). LCMS (ESI) m/z 489 (M+H)+.

Workup

  1. customArgon was bubbled into the mixture for 5 min
  2. customArgon was bubbled into the mixture for an additional 5 min
  3. temperaturethe mixture was heated in a sealed tube for 15 h
  4. custompartitioned between EtOAc (100 mL) and water (50 mL)
  5. customThe EtOAc layer was separated
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by reverse-phase preparative HPLC
  8. additiona mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase

Sources & evidence

ORD record
ord-8915672b092e492d8c1fc65eb2aeb82d
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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