Water → tert-butyl 4-(5-(7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl)pyrazin-2-yl)piperazine-1-carboxylate

HRID 2209194Notes

Reaction equation

HRID 2209194 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]([O:18][C@@H:19]([C@H:21]3[CH2:25][NH:24][C:23](=[O:26])[CH2:22]3)[CH3:20])[C:12]3[S:16][CH:15]=[N:14][C:13]=3[CH:17]=2)O1.I[C:29]1[N:30]=[CH:31][C:32]([N:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH2:36]2)=[N:33][CH:34]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[O:26]=[C:23]1[NH:24][CH2:25][C@H:21]([C@H:19]([O:18][C:11]2[C:12]3[S:16][CH:15]=[N:14][C:13]=3[CH:17]=[C:9]([C:29]3[N:30]=[CH:31][C:32]([N:35]4[CH2:36][CH2:37][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:39][CH2:40]4)=[N:33][CH:34]=3)[CH:10]=2)[CH3:20])[CH2:22]1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 866692291,1-Dimethylethyl 4-(5-iodo-2-pyrazinyl)-1-piperazinecarboxylateHCID 123174463(R)-4-((R)-1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-7-yloxy)ethyl)pyrrolidin-2-one

Product 1

HCID 117843214tert-butyl 4-(5-(7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl)pyrazin-2-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

(R)-4-((R)-1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-7-yloxy)ethyl)pyrrolidin-2-one 4.05 (40 mg, 0.10 mmol), tert-butyl 4-(5-iodopyrazin-2-yl)piperazine-1-carboxylate 7.11 (48 mg, 0.12 mmol), K3PO4 (65.6 mg, 0.31 mmol), and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (1.3 mg, 0.002 mmol) were taken up in 1,4-dioxane (1.5 mL) and water (0.15 mL) under Ar. The reaction mixture was stirred at 100° C. for 40 min and was then 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 (0-15% MeOH in DCM) to afford tert-butyl 4-(5-(7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl)pyrazin-2-yl)piperazine-1-carboxylate. LCMS-ESI+ (m/z): [M+H]+ calcd for C26H33N6O4S: 525.2; found: 524.9.

Workup

  1. customwas then partitioned between EtOAc, water, and brine
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with EtOAc
  4. dry with materialThe combined organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by silica gel chromatography (0-15% MeOH in DCM)

Sources & evidence

ORD record
ord-a9121dbc3ba8453f839769f1c87771ea
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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