Morpholine → (S)-2-fluoro-7-(2-fluoropyridin-3-yl)-3-morpholino-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

HRID 335970Notes

Reaction equation

HRID 335970 reaction equation
[F:1][C:2]1[N:7]=[C:6]2[O:8][C:9]3[C:14]([C@@:15]4([CH2:19][O:18][C:17]([NH2:20])=[N:16]4)[C:5]2=[CH:4][C:3]=1I)=[CH:13][C:12]([C:21]1[C:22]([F:27])=[N:23][CH:24]=[CH:25][CH:26]=1)=[CH:11][CH:10]=3.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C.CC(OC)(C)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].C1COCC1>[F:1][C:2]1[N:7]=[C:6]2[O:8][C:9]3[C:14]([C@@:15]4([CH2:19][O:18][C:17]([NH2:20])=[N:16]4)[C:5]2=[CH:4][C:3]=1[N:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)=[CH:13][C:12]([C:21]1[C:22]([F:27])=[N:23][CH:24]=[CH:25][CH:26]=1)=[CH:11][CH:10]=3

Participants

6

Reactant 3

HCID 8083MorpholineHCID 2733832Lithium HexamethyldisilazideHCID 58466247HCID 58466247, compound

Product 1

HCID 58466153(S)-2-fluoro-7-(2-fluoropyridin-3-yl)-3-morpholino-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amineYield 23.7%

Reagents, catalysts & solvents 2

HCID 66572931HCID 66572931, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A vial charged with (S)-2-fluoro-7-(2-fluoropyridin-3-yl)-3-iodo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (0.20 g, 0.41 mmol, prepared as described in Method BB34) and Ruphos palladacycle (0.032 g, 0.041 mmol) was treated with morpholine (0.18 mL, 2.03 mmol) and 4 mL THF. LiHMDS (2.03 mL, 2.03 mmol) was added, the vial was capped under argon, and the reaction mixture was allowed to stir overnight. The reaction mixture was purified directly by column chromatography [0-80% (9:1 DCM/MeOH)/heptane] yielding (S)-2-fluoro-7-(2-fluoropyridin-3-yl)-3-morpholino-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (0.044 g, 0.097 mmol). [M+H]+=452.0

Workup

  1. customthe vial was capped under argon
  2. customThe reaction mixture was purified directly by column chromatography [0-80% (9:1 DCM/MeOH)/heptane]

Sources & evidence

ORD record
ord-8bf7122cca71496b91911798e1c4d449
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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