Potassium Phosphate, Tribasic → (2S)-1-tert-butyl 2-methyl 4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-2H-pyrrole-1,2(5H)-dicarboxylate

HRID 1177533Notes

Reaction equation

HRID 1177533 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:9][C:10]1[CH:15]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:13]=[CH:12][C:11]=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.FC(F)(F)S(O[C:49]1[CH2:53][N:52]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[C@H:51]([C:61]([O:63][CH3:64])=[O:62])[CH:50]=1)(=O)=O>CN(C=O)C>[F:9][C:10]1[CH:15]=[C:14]([C:49]2[CH2:53][N:52]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[C@H:51]([C:61]([O:63][CH3:64])=[O:62])[CH:50]=2)[CH:13]=[CH:12][C:11]=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)[CH2:35][CH2:36]1)[N:28]=2

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 11773246(S)-1-tert-Butyl 2-methyl 4-(((trifluoromethyl)sulfonyl)oxy)-1H-pyrrole-1,2(2H,5H)-dicarboxylateHCID 671119352-(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine

Product 1

HCID 67112968(2S)-1-tert-butyl 2-methyl 4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-2H-pyrrole-1,2(5H)-dicarboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A slurry of potassium phosphate (2.50 g, 11.8 mmol), (Amphos)2PdCl2 (0.125 g, 0.177 mmol), 2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine (2.78 g, 5.89 mmol) and (S)-1-tert-butyl 2-methyl 4-(trifluoromethylsulfonyloxy)-1H-pyrrole-1,2(2H,5H)-dicarboxylate (2.21 g, 5.89 mmol, synthesized according to literature reference: Bioorganic and Medicinal Chemistry Letters, 2007, 2715) in 15 mL DMF was flushed with argon, sealed, and heated to 80° C. After 6 h, the reaction was judged complete, cooled, and filtered through celite, rinsing with 200 mL EtOAc. The filtrate was washed with water, brine, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by silica gel chromatography, EA/hexanes gradient, gave (2S)-1-tert-butyl 2-methyl 4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-2H-pyrrole-1,2(5H)-dicarboxylate as a light yellow solid. MS (ESI) m/z: Calculated: 571.2; Observed: 572.1 (M++1).

Workup

  1. customsealed
  2. temperaturecooled
  3. filtrationfiltered through celite
  4. washrinsing with 200 mL EtOAc
  5. washThe filtrate was washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by silica gel chromatography, EA/hexanes gradient

Sources & evidence

ORD record
ord-0ac67b9abfa9416a91daef1e78fe467a
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

Loading…