Triethylamine → HCID 178441314, compound

HRID 78551Notes

Reaction equation

HRID 78551 reaction equation
Br[C:2]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][C:3]=1[C:4](/[N:6]=[C:7]1\[S:8][C:9]([C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:10][N:11]\1[CH2:12][C@H:13]1[CH2:17][CH2:16][CH2:15][O:14]1)=[O:5].C(N(CC)CC)C.[CH3:37][S:38]([CH:41]=[CH2:42])(=[O:40])=[O:39].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:18]([C:9]1[S:8]/[C:7](=[N:6]\[C:4](=[O:5])[C:3]2[CH:22]=[C:23]([C:26]([F:29])([F:28])[F:27])[CH:24]=[CH:25][C:2]=2/[CH:42]=[CH:41]/[S:38]([CH3:37])(=[O:40])=[O:39])/[N:11]([CH2:12][C@H:13]2[CH2:17][CH2:16][CH2:15][O:14]2)[CH:10]=1)([CH3:21])([CH3:20])[CH3:19]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 19354Methyl vinyl sulfoneHCID 80271Tri-o-tolylphosphineHCID 178441313HCID 178441313, compound

Product 1

HCID 178441314HCID 178441314, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of Example 386B (172 mg, 0.350 mmol), triethylamine (53 mg, 0.525 mmol) and methylvinylsulfone (55.7 mg, 0.525 mmol) in acetonitrile (1 mL) was added palladium acetate (4.72 mg, 0.021 mmol) and tri(o-tolyl)phosphine (23.44 mg, 0.077 mmol). This mixture was heated in a microwave at 140° C. for 30 min. The reaction was heated another 30 min at 180° C. The reaction mixture was cooled to room temperature and filtered. The residue was purified by preparative HPLC on a Phenomenex Luna Combi-HTS C8(2) column (5 μm, 100 Å, 2.1 mm×30 mm), using a gradient of 10-100% acetonitrile (A) and 10 mM ammonium acetate in water (B), at a flow rate of 2.0 mL/min (0-0.1 min 10% A, 0.1-2.6 min 10-100% A, 2.6-2.9 min 100% A, 2.9-3.0 min 100-10% A. 0.5 min post-run delay) to provide the title compound (85 mg, 47%). 1H NMR (300 MHz, CDCl3) δ ppm 1.38 (s, 9H) 1.62-1.71 (m, 1H) 1.76-1.92 (m, 2H) 2.02-2.14 (m, 1H) 3.08 (s, 3H) 3.73-3.87 (m, 2H) 4.22-4.34 (m, 2H) 4.50 (d, J=11.10 Hz, 1H) 6.80 (d, J=15.47 Hz, 1H) 6.97 (s, 1H) 7.59-7.72 (m, 2H) 8.52 (s, 1H) 8.83 (d, J=15.47 Hz, 1H); MS (DCI/NH3) m/z 517 (M+H)+.

Workup

  1. temperatureThe reaction was heated another 30 min at 180° C
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered
  4. customThe residue was purified by preparative HPLC on a Phenomenex Luna Combi-HTS C8(2) column (5 μm, 100 Å, 2.1 mm×30 mm)

Sources & evidence

ORD record
ord-e836815f371543a28ef85a90ae2d7ee8
Source dataset
uspto-grants-2014_09
Patent number
US08841334B2

Reaction notes

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