(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 455639노트

반응식

HRID 455639 반응식
[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

참가 물질

3

반응물 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

생성물 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'-amine수율 86.7%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-60520fd648884a1db0a055f8a61e414b
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08497264B2

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