Ethyl Acetate → Ethyl 6-(2-(bis(tert-butoxycarbonyl)-amino)thiazol-5-yl)-8-phenylimidazo[1,2-a]pyridine-2-carboxylate

HRID 2197550Notes

Reaction equation

HRID 2197550 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:5]2[N:6]([CH:8]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:10]=2)[CH:7]=1.[C:22]([O:26][C:27]([N:29]([C:37]1[S:38][C:39](B2OC(C)(C)C(C)(C)O2)=[CH:40][N:41]=1)[C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:28])([CH3:25])([CH3:24])[CH3:23].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:22]([O:26][C:27]([N:29]([C:30]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:36])[C:37]1[S:38][C:39]([C:2]2[CH:3]=[C:4]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:5]3[N:6]([CH:8]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:10]=3)[CH:7]=2)=[CH:40][N:41]=1)=[O:28])([CH3:25])([CH3:24])[CH3:23]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 62657Potassium Phosphate, TribasicHCID 58208011Ethyl 6-bromo-8-phenylimidazo[1,2-a]pyridine-2-carboxylateHCID 67007586Tert-butyl (tert-butoxycarbonyl)(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazol-2-yl)carbamate

Product 1

HCID 58207967Ethyl 6-(2-(bis(tert-butoxycarbonyl)-amino)thiazol-5-yl)-8-phenylimidazo[1,2-a]pyridine-2-carboxylateYield 17.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of ethyl 6-bromo-8-phenylimidazo[1,2-a]pyridine-2-carboxylate (0.10 g, 0.29 mmol) and tert-butyl (tert-butoxycarbonyl)(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazol-2-yl)carbamate (0.14 g, 0.33 mmol) in toluene (3 mL) and ethanol (1 mL) was bubbled nitrogen for 20 mins. The mixture was then treated with Pd(PPh3)4 (30 mg, 0.026 mmol) and K3PO4 (2 M, 1 mL, 2 mmol) and heated at 80° C. overnight. The reaction was cooled, poured into ethyl acetate (200 mL), washed with brine, separated, and concentrated. The residue was purified by column chromatography using ethyl acetate in hexanes (10-30%) as eluent. The product containing fractions were concentrated to give 28 mg (15% yield) of ethyl 6-(2-(bis(tert-butoxycarbonyl)-amino)thiazol-5-yl)-8-phenylimidazo[1,2-a]pyridine-2-carboxylate as a white solid. LCMS (Conditions C): 4.15 min (RT); (M+H)+=565.62 (100%).

Workup

  1. temperatureThe reaction was cooled
  2. washwashed with brine
  3. customseparated
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography
  6. additionThe product containing fractions
  7. concentrationwere concentrated

Sources & evidence

ORD record
ord-5c0e407d72de43b686a38fb7b985c616
Source dataset
uspto-grants-2012_12
Patent number
US08338604B2

Reaction notes

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