Acetamidomalonic acid diethyl ester → Diethyl 2-acetamido-2-(2-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)ethyl)malonate

HRID 1177503Notes

Reaction equation

HRID 1177503 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[CH:5]([NH:11][C:12](=[O:14])[CH3:13])[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2].[F:16][C:17]1[CH:22]=[C:21]([CH:23]=[CH2:24])[CH:20]=[CH:19][C:18]=1[C:25]1[S:26][C:27]2[C:32]([N:33]=1)=[CH:31][CH:30]=[C:29]([C:34]1([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH2:36][CH2:35]1)[N:28]=2>CS(C)=O>[C:12]([NH:11][C:5]([CH2:24][CH2:23][C:21]1[CH:20]=[CH:19][C:18]([C:25]2[S:26][C:27]3[C:32]([N:33]=2)=[CH:31][CH:30]=[C:29]([C:34]2([C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)[CH2:35][CH2:36]2)[N:28]=3)=[C:17]([F:16])[CH:22]=1)([C:4]([O:3][CH2:1][CH3:2])=[O:15])[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:14])[CH3:13]

Participants

4

Reactant 2

HCID 14041Acetamidomalonic acid diethyl esterHCID 591749092-(2-Fluoro-4-vinylphenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine

Product 1

HCID 67111679Diethyl 2-acetamido-2-(2-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)ethyl)malonate

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
35 °C

Procedure

A slurry of CsCO3 (0.420 g, 1.29 mmol) and acetamidomalonic acid diethyl ester (0.560 g, 2.58 mmol) in 6 mL DMSO under argon was allowed to stir for 2 h. 2-(2-Fluoro-4-vinylphenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine (0.400 g, 1.07 mmol) was added as a solid and the reaction mixture sealed and heated to 35° C. for 3 h. The clear, red reaction mixture was quenched with ice and 1N aq. HCl until acidic, and partitioned between water and EA. The organic layer was washed with water, brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The material was treated with DCM and passed through a Redi-Sep® pre-packed silica gel column (40 g) using 0-60% EtOAc/hexane. The product-containing fractions were concentrated to afford diethyl 2-acetamido-2-(2-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)ethyl)malonate as a white solid. MS (ESI) m/z: calculated: 589.2; Observed: 590.1 (M++1).

Workup

  1. customthe reaction mixture sealed
  2. customThe clear, red reaction mixture was quenched with ice and 1N aq. HCl until acidic, and
  3. custompartitioned between water and EA
  4. washThe organic layer was washed with water, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. additionThe material was treated with DCM
  9. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-b9f9ac1904e54d38a5efe80615cbee74
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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