2-Thiazolamine, 5-bromo- → HCID 18393136, compound

HRID 1739729Notes

Reaction equation

HRID 1739729 reaction equation
[F:1][C:2]([F:31])([F:30])[C:3]1[CH:4]=[C:5]([C@H:13]([O:16][C@H:17]2[O:22][CH2:21][CH2:20][NH:19][C@H:18]2[C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH2:14][OH:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[NH2:32][C:33]1[S:34][C:35](Br)=[CH:36][N:37]=1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:31][C:2]([F:1])([F:30])[C:3]1[CH:4]=[C:5]([C@H:13]([O:16][C@H:17]2[O:22][CH2:21][CH2:20][N:19]([C:35]3[S:34][C:33]([NH2:32])=[N:37][CH:36]=3)[C@H:18]2[C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH2:14][OH:15])[CH:6]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:8]=1

Participants

7

Reactant 4

HCID 436002-Thiazolamine, 5-bromo-HCID 80271Tri-o-tolylphosphineHCID 22870743HCID 22870743, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 18393136HCID 18393136, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of 2-(R)-(1-(S)-(3,5-bis(trifluoromethyl) -phenyl)-2-hydroxyethoxy)-3-(S)-(4-fluorophenyl)morpholine (0.2 g), 2-amino-5-bromothiazole (0.14 g), sodium tert-butoxide (0.0105 g) and tri-o-tolylphosphine (0.007 g) in dioxane (4 ml) was added tris(dibenzylideneacetone)dipalladium (0) (0.02 g). The solution was degassed and then heated at 80° C. for 24 h under an atmosphere of nitrogen. The solvent was removed in vacuo and the residue partitioned between ethyl acetate and water. The organic layer was dried (MgSO4) and after evaporation of the solvent the residue was chromatographed on silica (eluting with gradient of 2% -4% methanol/ammonia (100:3) in dichloromethane) to give the title compound. 1H NMR (360 MHz, CDCl3) δ3.11 (1H, td, J=11.7 Hz, 3.5 Hz), 3.19 (1H, bd J=11.4 Hz), 3.61 (1H, dd, J=12.2 Hz and 3.3 Hz), 3.67-3.81 (3H, m), 4.47 (1H, d, J=2.8 Hz), 4.54 (1H, td, J=11.7 Hz and 2.8 Hz), 4.80 (2H, bs), 4.92 (1H, dd, J=7.8 Hz and 3.1 Hz), 6.97 (2H, t, J=8.7 Hz), 7.09 (1H, s), 7.14 (2H, s), 4.91 (1H, dd, J=7.8 Hz and 3.1 Hz), 7.67 (1H, s); m/z EI+ 552(M+H).

Workup

  1. customThe solution was degassed
  2. customThe solvent was removed in vacuo
  3. customthe residue partitioned between ethyl acetate and water
  4. dry with materialThe organic layer was dried (MgSO4)
  5. customafter evaporation of the solvent the residue
  6. customwas chromatographed on silica (eluting with gradient of 2% -4% methanol/ammonia (100:3) in dichloromethane)

Sources & evidence

ORD record
ord-6eb8a7b1c8d842698bd143066c2dde39
Source dataset
uspto-grants-1999_10
Patent number
US05968934

Reaction notes

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