Cesium carbonate → HCID 86270538, compound

HRID 527999Notes

Reaction equation

HRID 527999 reaction equation
Cl[C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[CH2:12][CH2:13][N:14]([S:17]([CH3:20])(=[O:19])=[O:18])[CH2:15][CH:16]=3)[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:21][C:22]1[CH:23]=[C:24]([CH3:32])[C:25]([F:31])=[C:26](B(O)O)[CH:27]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[Ca+2].[Ca+2].[Ca+2]>C(O)C.[Pd]>[Cl:21][C:22]1[CH:23]=[C:24]([CH3:32])[C:25]([F:31])=[C:26]([C:2]2[C:3]3[CH:10]=[C:9]([C:11]4[CH2:12][CH2:13][N:14]([S:17]([CH3:20])(=[O:19])=[O:18])[CH2:15][CH:16]=4)[NH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:27]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 24456Tricalcium PhosphateHCID 16217160(5-Chloro-2-fluoro-3-methylphenyl)boronic acidHCID 90418872HCID 90418872, compound

Product 1

HCID 86270538HCID 86270538, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent2×

Conditions

Temperature
120 °C

Procedure

A 4 mL vial was charged with a stir bar, a solution of Example 41A (27.50 mg, 0.09 mmol) in 1 mL of ethanol, a solution of (5-chloro-2-fluoro-3-methylphenyl)boronic acid (24.85 mg, 1.5 eq, 0.13 mmol) in 220 μL of ethanol, a 1.0 M aqueous solution of cesium carbonate (175.84 μL, 2 eq, 0.18 mmol), and Siliacat® DPP-Pd (Silicycle®, 0.27 mmol/g loading, 32.56 mg). The loaded vial was seal capped and placed in an Anton Paar Synthos 3000 microwave reactor (900 W maximum) and heated to 120° C. for 15 minutes. Upon completion, the solids were collected by filtration and dried under vacuum. The dried material was then re-dissolved in 1.4 mL of dimethyl sulfoxide/methanol 1:1 (v/v) solution, and purified by preparative HPLC on a Phenomenex® Luna® C8(2) 5 μm 100A AXIA™ column (30 mm×75 mm) A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 50 mL/minute (0-0.5 minutes 10% A, 0.5-6.0 minutes linear gradient 10-100% A, 6.0-7.0 minutes 100% A, 7.0-8.0 minutes linear gradient 100-10% A) to yield the title compound. 1H NMR (400 MHz, DMSO-d6/D2O) δ 2.37 (d, J=2.1 Hz, 3H), 2.65 (s, 2H), 2.95 (d, J=5.2 Hz, 3H), 3.18 (s, 1H), 3.40 (t, J=5.7 Hz, 2H), 3.95 (d, J=3.4 Hz, 2H), 6.57 (d, J=3.8 Hz, 1H), 6.59-6.64 (m, 1H), 7.60 (d, J=5.8 Hz, 2H), 8.85 (s, 1H). MS (ESI+) m/z 421.1 (M+H)+. Examples 42 through 59 were prepared essentially as described in Example 41B, substituting the appropriate boronic acid.

Workup

  1. additionA 4 mL vial was charged with a stir bar
  2. customThe loaded vial was seal
  3. customcapped
  4. filtrationUpon completion, the solids were collected by filtration
  5. customdried under vacuum
  6. dissolutionThe dried material was then re-dissolved in 1.4 mL of dimethyl sulfoxide/methanol 1:1 (v/v) solution
  7. custompurified by preparative HPLC on a Phenomenex® Luna® C8(2) 5 μm 100A AXIA™ column (30 mm×75 mm) A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B)
  8. customwas used, at a flow rate of 50 mL/minute (0-0.5 minutes 10% A, 0.5-6.0 minutes linear gradient 10-100% A, 6.0-7.0 minutes 100% A, 7.0-8.0 minutes linear gradient 100-10% A)

Sources & evidence

ORD record
ord-0760f4b404e94fe3b3edfaeef8eeeb74
Source dataset
uspto-grants-2016_05
Patent number
US09346813B2

Reaction notes

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