18-Crown-6 → (S)-2-fluoro-7-(2-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

HRID 335971Notes

Reaction equation

HRID 335971 reaction equation
C1OCCOCCOCCOCCOCCOC1.[F-].[K+].[F:21][C:22]1[N:27]=[C:26]2[O:28][C:29]3[C:34]([C@@:35]4([CH2:39][O:38][C:37]([NH2:40])=[N:36]4)[C:25]2=[CH:24][C:23]=1I)=[CH:33][C:32]([C:41]1[C:42]([F:47])=[N:43][CH:44]=[CH:45][CH:46]=1)=[CH:31][CH:30]=3.C[Si](C)(C)[C:51]#[C:52][C:53]1([CH3:57])[CH2:56][O:55][CH2:54]1>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.[Cu]I.CN(C=O)C>[F:21][C:22]1[N:27]=[C:26]2[O:28][C:29]3[C:34]([C@@:35]4([CH2:39][O:38][C:37]([NH2:40])=[N:36]4)[C:25]2=[CH:24][C:23]=1[C:51]#[C:52][C:53]1([CH3:57])[CH2:56][O:55][CH2:54]1)=[CH:33][C:32]([C:41]1[C:42]([F:47])=[N:43][CH:44]=[CH:45][CH:46]=1)=[CH:31][CH:30]=3

Participants

8

Reactant 4

HCID 2855718-Crown-6HCID 522689Potassium FluorideHCID 58466247HCID 58466247, compoundHCID 58547788Trimethyl((3-methyloxetan-3-yl)ethynyl)silane

Product 1

HCID 53464256(S)-2-fluoro-7-(2-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amineYield 67.7%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A vial charged with Pd(Ph3P)4 (0.035 g, 0.030 mmol), copper(I) iodide (5.80 mg, 0.030 mmol), 18-crown-6 (0.12 g, 0.46 mmol), potassium fluoride (0.035 g, 0.61 mmol), (S)-2-fluoro-7-(2-fluoropyridin-3-yl)-3-iodo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (0.15 g, 0.31 mmol, prepared as described in Method BB34), and trimethyl((3-methyloxetan-3-yl)ethynyl)silane (0.077 g, 0.46 mmol) was treated with 1.5 mL DMF, capped under argon, and was heated to 100° C. for 2 h. The reaction mixture was purified directly by column chromatography [0-100% (95:5 EtOAc/MeOH)/hexanes] yielding (S)-2-fluoro-7-(2-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (0.095 g, 0.206 mmol, 67.7% yield). MS m/z=461.0 [M+H]+. Calculated for C25H18F2N4O3: 460.43.

Workup

  1. customcapped under argon
  2. customThe reaction mixture was purified directly by column chromatography [0-100% (95:5 EtOAc/MeOH)/hexanes]

Sources & evidence

ORD record
ord-ee6d6b9f1756415fb8ec1ee3f5c988a2
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

Loading…