(S)-3-(3,6-dihydro-2H-pyran-4-yl)-7-(2-fluoropyridin-3-yl)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine → (S)-7-(2-fluoropyridin-3-yl)-3-(tetrahydro-2H-pyran-4-yl)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine

HRID 455639Notes

Reaction equation

HRID 455639 reaction equation
[O:1]1[CH2:6][CH:5]=[C:4]([C:7]2[N:12]=[CH:11][C:10]3[O:13][C:14]4[C:19]([C@:20]5([N:25]=[C:24]([NH2:26])[CH2:23][O:22][CH2:21]5)[C:9]=3[CH:8]=2)=[CH:18][C:17]([C:27]2[C:28]([F:33])=[N:29][CH:30]=[CH:31][CH:32]=2)=[CH:16][CH:15]=4)[CH2:3][CH2:2]1>CO>[F:33][C:28]1[C:27]([C:17]2[CH:18]=[C:19]3[C@:20]4([N:25]=[C:24]([NH2:26])[CH2:23][O:22][CH2:21]4)[C:9]4[CH:8]=[C:7]([CH:4]5[CH2:5][CH2:6][O:1][CH2:2][CH2:3]5)[N:12]=[CH:11][C:10]=4[O:13][C:14]3=[CH:15][CH:16]=2)=[CH:32][CH:31]=[CH:30][N:29]=1

Participants

3

Reactant 1

HCID 67438959(S)-3-(3,6-dihydro-2H-pyran-4-yl)-7-(2-fluoropyridin-3-yl)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine

Product 1

HCID 67437145(S)-7-(2-fluoropyridin-3-yl)-3-(tetrahydro-2H-pyran-4-yl)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amineYield 86.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 10-mL round-bottom flask was charged with (S)-3-(3,6-dihydro-2H-pyran-4-yl)-7-(2-fluoropyridin-3-yl)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (82.8 mg, 0.186 mmol) and MeOH (2.5 mL). The flask was flushed with Ar (g), then 10% Pd/C (ca. 35 mg) was added. H2 (g) was bubbled through the mixture for 1 min, then the reaction mixture was stirred under an H2 (g) atmosphere overnight. An additional portion of 10% Pd/C (21 mg) was added, and H2 (g) was bubbled through for 1 min. After stirring overnight, the mixture was filtered through celite, and the filter cake was washed with methanol. The filtrate was concentrated, and the residue was purified by chromatography (10-40% of a 90:10:1 mixture of DCM/MeOH/NH4OH in DCM) to give (S)-7-(2-fluoropyridin-3-yl)-3-(tetrahydro-2H-pyran-4-yl)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (72 mg) as an off-white solid. [M+H]+=447.2.

Workup

  1. customThe flask was flushed with Ar (g)
  2. addition10% Pd/C (ca. 35 mg) was added
  3. customH2 (g) was bubbled through the mixture for 1 min
  4. additionAn additional portion of 10% Pd/C (21 mg) was added
  5. customH2 (g) was bubbled through for 1 min
  6. stirringAfter stirring overnight
  7. filtrationthe mixture was filtered through celite
  8. washthe filter cake was washed with methanol
  9. concentrationThe filtrate was concentrated
  10. customthe residue was purified by chromatography (
  11. addition10-40% of a 90:10:1 mixture of DCM/MeOH/NH4OH in DCM)

Sources & evidence

ORD record
ord-60520fd648884a1db0a055f8a61e414b
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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