Tetrabutylammonium Fluoride Trihydrate → 5',6'-Dihydrospiro[chromeno[2,3-b]pyridine-5,4'-[1,3]oxazin]-2'-amine

HRID 1472440Notes

Reaction equation

HRID 1472440 reaction equation
O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C[Si](C)(C)C#CC1(C)COC1.Br[C:34]1[CH:35]=[C:36]2[C@:47]3([CH2:52][CH2:51][O:50][C:49]([NH2:53])=[N:48]3)[C:46]3[C:41](=[CH:42][CH:43]=[C:44](C4C(F)=NC=CC=4)[CH:45]=3)[O:40][C:37]2=[N:38][CH:39]=1>C1COCC1.CO.CCOC(C)=O.[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>[O:50]1[CH2:51][CH2:52][C:47]2([C:36]3[C:37](=[N:38][CH:39]=[CH:34][CH:35]=3)[O:40][C:41]3[C:46]2=[CH:45][CH:44]=[CH:43][CH:42]=3)[N:48]=[C:49]1[NH2:53]

Participants

8

Reactant 3

HCID 11726816Tetrabutylammonium Fluoride TrihydrateHCID 58465877(S)-3-bromo-7-(2-fluoropyridin-3-yl)-5',6'-dihydrospiro[chromeno[2,3-b]pyridine-5,4'-[1,3]oxazin]-2'-amineHCID 58547788Trimethyl((3-methyloxetan-3-yl)ethynyl)silane

Product 1

HCID 1317327555',6'-Dihydrospiro[chromeno[2,3-b]pyridine-5,4'-[1,3]oxazin]-2'-amineYield 72%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 21584119Ethylacetate methanolSolvent

Conditions

Temperature
80 °C

Procedure

In a microwave vial, tetrabutylammonium fluoride trihydrate (0.059 g, 0.187 mmol), trimethyl((3-methyloxetan-3-yl)ethynyl)silane (0.031 g, 0.187 mmol), copper(I) iodide (2.374 mg, 0.012 mmol), Pd(PPh3)4 (0.014 g, 0.012 mmol), and (S)-3-bromo-7-(2-fluoropyridin-3-yl)-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-2′-amine (0.055 g, 0.125 mmol) were suspended in THF (1.25 mL). Argon gas was blown through the vessel, which was sealed and heated in an 80° C. oil bath for 1.5 h. The mixture was taken up in 10% MeOH-EtOAc (60 mL) and the organic layer was extracted with dilute brine (8 mL) then with saturated brine (8 mL), dried over sodium sulfate and concentrated. The residue was purified by chromatography (5% MeOH/DCM), to afford (S)-7-(2-fluoropyridin-3-yl)-3-(3-methyloxetan-3-yl)ethynyl)-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-2′-amine (41 mg, 0.09 mmol). MS (m/z) 457 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm: 8.32 (d, 1 H, J=2.0 Hz), 8.20 (d, 1 H, J=4.9 Hz), 7.90 (m, 1 H), 7.78 (s, 1 H), 7.53 (m, 2 H), 7.38 (d, 1 H, J=8.4 Hz), 7.27 (m, 1 H), 4.94 (d, 2 H, J=5.3 Hz), 4.50 (d, 2 H, J=5.5 Hz), 4.44 (br, 2 H), 4.28 (m, 2 H), 1.95 (m, 1 H), 1.85 (m, 1 H), 1.74 (s, 3 H).

Workup

  1. customwas sealed
  2. extractionthe organic layer was extracted with dilute brine (8 mL)
  3. dry with materialwith saturated brine (8 mL), dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by chromatography (5% MeOH/DCM)

Sources & evidence

ORD record
ord-970dc890908d4f62b512ad57c96d51a5
Source dataset
uspto-grants-2015_04
Patent number
US09012446B2

Reaction notes

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