Sodium t-butoxide → HCID 86719505, compound

HRID 1772265Notes

Reaction equation

HRID 1772265 reaction equation
Br[C:2]1[S:3][C:4]2[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][C:5]=2[N:6]=1.CC(C)([O-])C.[Na+].Cl.[N+:22]([C:25]1[CH:30]=[CH:29][C:28]([NH:31][CH:32]2[CH2:37][CH2:36][CH:35]([O:38][CH2:39][C:40]([N:42]3[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]3)=[O:41])[CH2:34][CH2:33]2)=[CH:27][C:26]=1[C:48]([F:51])([F:50])[F:49])([O-:24])=[O:23]>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].C(Cl)(Cl)Cl.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>[N+:22]([C:25]1[CH:30]=[CH:29][C:28]([NH:31][CH:32]2[CH2:33][CH2:34][CH:35]([O:38][CH2:39][C:40]([N:42]3[CH2:47][CH2:46][N:45]([C:2]4[S:3][C:4]5[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][C:5]=5[N:6]=4)[CH2:44][CH2:43]3)=[O:41])[CH2:36][CH2:37]2)=[CH:27][C:26]=1[C:48]([F:51])([F:50])[F:49])([O-:24])=[O:23]

Participants

7

Reactant 3

HCID 23676156Sodium t-butoxideHCID 86719503HCID 86719503, compoundHCID 867195062-Bromo-5-trifluoromethylbenzothiazole

Product 1

HCID 86719505HCID 86719505, compoundYield 74.9%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 2-bromo-5-trifluoromethyl-benzothiazole (430 mg, 1.4 mmol, 1 eq.) in toluene (15 ml) was added sodium tert-butoxide (546 mg, 5.7 mmol, 4 eq.), BINAP (10 mg, 0.015 mmol, 0.01 eq.) and 2-[4-(4-nitro-3-trifluoromethyl-phenylamino)-cyclohexyloxy]-1-piperazin-1-yl-ethanone hydrochloride (1.33 g, 2.84 mmol, 2 eq.). The solution was flushed with nitrogen and evacuated three times before adding Pd2(dba)3-CHCl3 (31 mg, 0.03 mmol, 0.02 eq.) and flushing/evacuating a final time. The slurry was heated to for 18 hours at 70° C. before concentrating in vacuo. The residue was applied onto a silica gel column and eluted with Heptanes/EtOAc to afford 2-[4-(4-nitro-3-trifluoromethyl-phenylamino)-cyclohexyloxy]-1-[4-(5-trifluoromethyl-benzothiazol-2-yl)-piperazin-1-yl]-ethanone as a yellow solid (662 mg, 73.8%). (CI, m/z): [M+H]+ 632; 1H NMR (400 MHz, CDCl3): δ 1.29-1.38 (m, 2H), 1.41-1.56 (m, 2H), 2.16 (d, J=8.9 Hz, 4H), 3.26-3.53 (m, 2H), 3.55-3.90 (m, 8H), 4.26 (s, 2H), 4.47 (d, J=7.6 Hz, 1H), 6.63 (dd, J=9.1, 2.5 Hz, 1H), 6.85 (d, J=2.3 Hz, 1H), 7.36 (d, J=8.2 Hz, 1H), 7.72 (d, J=8.2 Hz, 1H), 7.81 (s, 1H), 8.01 (d, J=9.0 Hz, 1H).

Workup

  1. customThe solution was flushed with nitrogen
  2. customevacuated three times
  3. customflushing/evacuating a final time
  4. concentrationbefore concentrating in vacuo
  5. washeluted with Heptanes/EtOAc

Sources & evidence

ORD record
ord-cb323ff82e884d7fbb8db5f444d7f15d
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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