Potassium Phosphate, Tribasic → tert-butyl 4-(2-methoxy-4-(7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl)phenyl)piperazine-1-carboxylate

HRID 2209190Notes

Reaction equation

HRID 2209190 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]([O:16][C@@H:17]([C@@H:19]2[CH2:23][C:22](=[O:24])[NH:21][CH2:20]2)[CH3:18])[C:10]2[S:14][CH:13]=[N:12][C:11]=2[CH:15]=1)(=O)=O.[CH3:27][O:28][C:29]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[CH:31][C:30]=1[N:44]1[CH2:49][CH2:48][N:47]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:46][CH2:45]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1COCC1.CC([O-])=O.CC([O-])=O.[Pd+2].O>[CH3:27][O:28][C:29]1[CH:34]=[C:33]([C:7]2[CH:8]=[C:9]([O:16][C@@H:17]([C@@H:19]3[CH2:23][C:22](=[O:24])[NH:21][CH2:20]3)[CH3:18])[C:10]3[S:14][CH:13]=[N:12][C:11]=3[CH:15]=2)[CH:32]=[CH:31][C:30]=1[N:44]1[CH2:45][CH2:46][N:47]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:48][CH2:49]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 89494488Tert-butyl 4-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylateHCID 1178434547-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl trifluoromethanesulfonate

Product 1

HCID 117843499tert-butyl 4-(2-methoxy-4-(7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl)phenyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl trifluoromethanesulfonate (4.04) (100.7 mg, 0.245 mmol), tert-butyl 4-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylate 7.08 (144 mg, 0.344 mmol), Pd(OAc)2 (2.8 mg, 0.012 mmol), 2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (12 mg 0.025 mmol), and K3PO4 (155 mg, 0.73 mmol) were taken up in THF (3.6 mL) under Ar. Water (0.36 mL) was added and the resulting stirred mixture was heated to 65° C. After 1.25 h, the reaction mixture was cooled and was partitioned between EtOAc, water, and brine. The phases were separated, and the aqueous phase was extracted with EtOAc. The combined organic phase was dried over Na2SO4, filtered, and concentrated. The crude residue was purified by silica gel chromatography to afford tert-butyl 4-(2-methoxy-4-(7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl)phenyl)piperazine-1-carboxylate. LCMS-ESI+ (m/z): [M+H]+ calcd for C29H37N4O5S: 553.3; found: 552.8.

Workup

  1. temperaturethe reaction mixture was cooled
  2. customwas partitioned between EtOAc, water, and brine
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with EtOAc
  5. dry with materialThe combined organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-08e8bbac787b4d95a8e569b027abcabb
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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