Cesium carbonate → HCID 86624187, compound

HRID 1191152Notes

Reaction equation

HRID 1191152 reaction equation
[CH:1]1([C:4]([NH:6][C:7]2[S:8][CH:9]=[C:10]([C:12]3[CH:19]=[CH:18][C:15]([CH2:16][NH2:17])=[CH:14][CH:13]=3)[N:11]=2)=[O:5])[CH2:3][CH2:2]1.[Cl:20][C:21]1[CH:37]=[CH:36][C:24]2[CH2:25][CH2:26][N:27]([C:30](=[O:35])[C:31]([F:34])([F:33])[F:32])[CH2:28][CH2:29][C:23]=2[C:22]=1OS(C(F)(F)F)(=O)=O.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:20][C:21]1[CH:37]=[CH:36][C:24]2[CH2:25][CH2:26][N:27]([C:30](=[O:35])[C:31]([F:32])([F:34])[F:33])[CH2:28][CH2:29][C:23]=2[C:22]=1[NH:17][CH2:16][C:15]1[CH:14]=[CH:13][C:12]([C:10]2[N:11]=[C:7]([NH:6][C:4]([CH:1]3[CH2:3][CH2:2]3)=[O:5])[S:8][CH:9]=2)=[CH:19][CH:18]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 59828900HCID 59828900, compound

Product 1

HCID 86624187HCID 86624187, compoundYield 19.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a slurry of 4-[2-(cyclopropanecarbonyl-amino)-thiazol-4-yl]-benzylamine (1.654 g, 6.052 mmol) in toluene (30.2 mL)/dioxane (7.8 mL), at 100° C., add a solid mixture of 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (1.29 g, 3.03 mmol), tris(dibenzylideneacetone)-dipalladium(0) (0.55 g, 0.61 mmol), BINAP (0.75 g, 0.12 mmol) and cesium carbonate (3.45 g, 10.6 mmol) all at once. Purge the reaction mixture with nitrogen and heat at 100° C. overnight. After cooling to room temperature, filter the reaction mixture over Celite® and wash with DCM (500 mL). Concentrate in vacuo, dissolve the residue in DCM and load on to an Analogix® column (150 g). Purify by preparative liquid chromatography (0:1 to 1:9 2M ammonia in methanol/DCM over 33 min, 1:9 to 1:3 2M ammonia in methanol/DCM over 33 min, 1:3 to 1:1 2M ammonia in methanol/DCM over 33 min; 35 mL/min) to afford 7-chloro-6-{4-[2-(cyclopropanecarbonyl-amino)-thiazol-4-yl]-benzylamino}-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.318 g, 19%) as a yellow foam. MS (ES+) m/z: 549.1 (M+H)+.

Workup

  1. customPurge the reaction mixture with nitrogen
  2. temperatureAfter cooling to room temperature
  3. filtrationfilter the reaction mixture over Celite®
  4. washwash with DCM (500 mL)
  5. concentrationConcentrate in vacuo
  6. dissolutiondissolve the residue in DCM
  7. customPurify by preparative liquid chromatography (0:1 to 1:9 2M ammonia in methanol/DCM over 33 min, 1:9 to 1:3 2M ammonia in methanol/DCM over 33 min, 1:3 to 1:1 2M ammonia in methanol/DCM over 33 min; 35 mL/min)

Sources & evidence

ORD record
ord-edf3cf5917b94d5d890074109b5dbd74
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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