Potassium Carbonate → (S)-3-(5,6-dihydro-2H-pyran-3-yl)-7-(5-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

HRID 335988Notes

Reaction equation

HRID 335988 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C@:15]3([CH2:19][S:18][C:17]([NH2:20])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:21]4[CH:22]=[N:23][CH:24]=[C:25]([F:27])[CH:26]=4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[O:34]1[CH2:39][CH2:38][CH:37]=[C:36](B2OC(C)(C)C(C)(C)O2)[CH2:35]1.O1CCOCC1>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.CO.O>[O:34]1[CH2:39][CH2:38][CH:37]=[C:36]([C:2]2[CH:3]=[C:4]3[C@:15]4([CH2:19][S:18][C:17]([NH2:20])=[N:16]4)[C:14]4[C:9](=[CH:10][CH:11]=[C:12]([C:21]5[CH:22]=[N:23][CH:24]=[C:25]([F:27])[CH:26]=5)[CH:13]=4)[O:8][C:5]3=[N:6][CH:7]=2)[CH2:35]1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 158366332-(5,6-dihydro-2H-pyran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 67438965(S)-3-bromo-7-(5-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

Product 1

HCID 58466289(S)-3-(5,6-dihydro-2H-pyran-3-yl)-7-(5-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amineYield 50%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with (S)-3-bromo-7-(5-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine (90 mg, 0.20 mmol), potassium carbonate (140 mg, 1.02 mmol), 2-(5,6-dihydro-2H-pyran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (85 mg, 0.41 mmol), tetrakis(triphenylphosphine)palladium(0) (23.46 mg, 0.020 mmol), dioxane (1.35 mL) and water (0.68 mL). The reaction was heated in the microwave at 100° C. for 40 min. After cooling for rt, the organic layer was separated with a separatory funnel, dried over sodium sulfate, filtered, and concentrated to afford a yellow oil which was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (12 g), 0-100% EtOAc in 90:10 CH2Cl2:CH3OH to provide a white solid, (S)-3-(5,6-dihydro-2H-pyran-3-yl)-7-(5-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine (45 mg, 0.10 mmol, 50% yield). MS m/z=447.2 [M+H]+. Calc'd for C24H19FN4O2S: 446.5.

Workup

  1. temperatureAfter cooling for rt
  2. customthe organic layer was separated with a separatory funnel
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford a yellow oil which
  7. customwas purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (12 g), 0-100% EtOAc in 90:10 CH2Cl2

Sources & evidence

ORD record
ord-d11321cf7c9a49a1b090494d97825ca1
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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