Benzyl mercaptan → HCID 86687553, compound

HRID 1473498Notes

Reaction equation

HRID 1473498 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=3[O:23][CH3:24])=[N:7][NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[SH:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>O1CCOCC1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH2:35]([S:34][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=3[O:23][CH3:24])=[N:7][NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

7

Reactant 3

HCID 7509Benzyl mercaptanHCID 81531DiisopropylethylamineHCID 86687554HCID 86687554, compound

Product 1

HCID 86687553HCID 86687553, compoundYield 60.1%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a pressure tube containing a solution of 7-bromo-4-(2-methoxy-4-(trifluoromethyl)phenyl)phthalazin-1(2H)-one (1.14 g, 2.86 mmol) and N,N-diisopropylethylamine (0.99 mL, 5.71 mmol) in 1,4-dioxane (20 mL) was added XantPhos (0.083 g, 0.143 mmol) and tris(dibenzylideneacetone) dipalladium (0) (0.065 g, 0.071 mmol) followed by (mercaptomethyl)benzene (0.352 mL, 3.00 mmol). The reaction tube was purged with nitrogen. The tube was sealed and heated at 80° C. for 30 min. After cooling to RT, the reaction was filtered over a pad of diatomaceous earth, rinsing well with EtOAc. The filtrate was concentrated. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a silica gel column (120 g), eluting with a gradient of 0% to 50% EtOAc in heptane, to provide 7-(benzylthio)-4-(2-methoxy-4-(trifluoromethyl)phenyl)phthalazin-1(2H)-one (0.76 g, 60% yield) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ ppm 3.77 (s, 3H), 4.44 (s, 2H), 7.15 (d, J=8.55 Hz, 1H), 7.21-7.28 (m, 1H), 7.32 (t, J=7.43 Hz, 2H), 7.40-7.50 (m, 4H), 7.57 (d, J=7.69 Hz, 1H), 7.72 (dd, J=8.60, 2.08 Hz, 1H), 8.11 (d, J=1.92 Hz, 1H), 12.85 (s, 1H). m/z (ESI) 443.0 (M+H)+.

Workup

  1. customThe reaction tube was purged with nitrogen
  2. customThe tube was sealed
  3. temperatureAfter cooling to RT
  4. filtrationthe reaction was filtered over a pad of diatomaceous earth
  5. washrinsing well with EtOAc
  6. concentrationThe filtrate was concentrated
  7. customThe crude material was absorbed onto a plug of silica gel
  8. custompurified by chromatography through a silica gel column (120 g)
  9. washeluting with a gradient of 0% to 50% EtOAc in heptane

Sources & evidence

ORD record
ord-7b5f2fd6acc14ae88fc3a5ca1470d377
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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