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

HRID 335994Notes

Reaction equation

HRID 335994 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[C:22]([F:27])=[N:23][CH:24]=[CH:25][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][CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH2:36][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[CH2:35][CH:36]=[C:37]([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[C:22]([F:27])=[N:23][CH:24]=[CH:25][CH:26]=5)[CH:13]=4)[O:8][C:5]3=[N:6][CH:7]=2)[CH2:38][CH2:39]1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 67438436(S)-3-bromo-7-(2-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

Product 1

HCID 53464448(S)-3-(3,6-dihydro-2H-pyran-4-yl)-7-(2-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amineYield 83%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vessel was charged with (S)-3-bromo-7-(2-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine (0.12 g, 0.27 mmol), potassium carbonate (0.19 g, 1.35 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.11 g, 0.54 mmol), tetrakis(triphenylphosphine)palladium(0) (0.031 g, 0.027 mmol), dioxane (1.81 mL) and water (0.90 mL). The reaction was heated in a microwave at 100° C. for 45 min. After cooling to 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 (40 g), 0-100% EtOAc in 90/10 CH2Cl2:CH3OH to provide a white solid, (S)-3-(3,6-dihydro-2H-pyran-4-yl)-7-(2-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine (0.1 g, 0.22 mmol, 83% yield). MS m/z=447.2 [M+H]+. Calc'd for C24H19FN4O2S: 446.5.

Workup

  1. temperatureAfter cooling to 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 (40 g), 0-100% EtOAc in 90/10 CH2Cl2

Sources & evidence

ORD record
ord-0d00b6cbc3de432491fc7837f7c583f2
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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