Dimethylformamide → (S)-7-(4-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

HRID 335990Notes

Reaction equation

HRID 335990 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]=[CH:25][C:26]=4[F:27])[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.CN(C=O)C.C[Si](C)(C)[C:35]#[C:36][C:37]1([CH3:41])[CH2:40][O:39][CH2:38]1>[Cu]I.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>[F:27][C:26]1[CH:25]=[CH:24][N:23]=[CH:22][C:21]=1[C:12]1[CH:13]=[C:14]2[C@@:15]3([CH2:19][S:18][C:17]([NH2:20])=[N:16]3)[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:35]#[C:36][C:37]4([CH3:41])[CH2:40][O:39][CH2:38]4)[CH:3]=3)[O:8][C:9]2=[CH:10][CH:11]=1

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 58547788Trimethyl((3-methyloxetan-3-yl)ethynyl)silaneHCID 67438006(S)-3-bromo-7-(4-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

Product 1

HCID 58466316(S)-7-(4-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amineYield 28.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Procedure

A vial was charged with (S)-3-bromo-7-(4-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine (120 mg, 0.27 mmol), copper(I) iodide (20.62 mg, 0.11 mmol), and tetrakis(triphenylphosphine)palladium (31.3 mg, 0.027 mmol). The vial was flushed with Ar (g), then DMF (1 mL), and trimethyl((3-methyloxetan-3-yl)ethynyl)silane (137 mg, 0.81 mmol), DIPA (574 μL, 4.06 mmol) were added in sequence. The vial was flushed with Ar (g), sealed, and placed in a 90° C. oil bath. The mixture was stirred overnight. After cooling to rt, the crude was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-80% EtOAc in 90:10 CH2Cl2:CH3OH to provide a white solid, (S)-7-(4-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine (35 mg, 0.076 mmol, 28% yield).

Workup

  1. customThe vial was flushed with Ar (g)
  2. customThe vial was flushed with Ar (g)
  3. customsealed
  4. customplaced in a 90° C.
  5. customthe crude was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-80% EtOAc in 90:10 CH2Cl2

Sources & evidence

ORD record
ord-2a1fd661bbca47ad8d6093530b7e9e48
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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