Water → tert-butyl 4-(2-methoxy-6-(7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl)pyridin-3-yl)piperazine-1-carboxylate

HRID 2209192Notes

Reaction equation

HRID 2209192 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.Cl[C:29]1[N:34]=[C:33]([O:35][CH3:36])[C:32]([N:37]2[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38]2)=[CH:31][CH:30]=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>[CH3:36][O:35][C:33]1[C:32]([N:37]2[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38]2)=[CH:31][CH:30]=[C:29]([C:9]2[CH:10]=[C:11]([O:18][C@@H:19]([C@@H:21]3[CH2:22][C:23](=[O:26])[NH:24][CH2:25]3)[CH3:20])[C:12]3[S:16][CH:15]=[N:14][C:13]=3[CH:17]=2)[N:34]=1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 117843574Tert-butyl 4-(6-chloro-2-methoxypyridin-3-yl)piperazine-1-carboxylateHCID 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 117844022tert-butyl 4-(2-methoxy-6-(7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl)pyridin-3-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) (43 mg, 0.11 mmol), tert-butyl 4-(6-chloro-2-methoxypyridin-3-yl)piperazine-1-carboxylate 7.10 (50 mg, 0.15 mmol), K3PO4 (70.5 mg, 0.33 mmol), and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (1.8 mg, 0.003 mmol) were taken up in 1,4-dioxane (1.6 mL) and water (0.16 mL) under Ar. The reaction mixture was stirred at 100° C. for 1.5 h and was then partitioned between EtOAc, water, and brine. The phases were separated, and the aqueous phase was dried over Na2SO4, filtered, and concentrated. The crude residue was purified to afford tert-butyl 4-(2-methoxy-6-(7-((R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)benzo[d]thiazol-5-yl)pyridin-3-yl)piperazine-1-carboxylate. LCMS-ESI+ (m/z): [M+H]+ calcd for C28H36N5O5S: 554.2; found: 554.5.

Workup

  1. customwas then partitioned between EtOAc, water, and brine
  2. customThe phases were separated
  3. dry with materialthe aqueous phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified

Sources & evidence

ORD record
ord-0a8eb86696964cecbf69686327208803
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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