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Potassium Carbonate → (S)-7-(2-fluoropyridin-3-yl)-3-(neopentyloxy)-2',6'-dihydrospiro[chromeno[2,3-b]pyridine-5,3'-[1,4]oxazin]-5'-amine

HRID 455680
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HRID 455680 반응식
[NH2:1][C:2]1[CH2:7][O:6][CH2:5][C@:4]2([C:20]3[C:15](=[N:16][CH:17]=[C:18]([OH:21])[CH:19]=3)[O:14][C:13]3[C:8]2=[CH:9][C:10]([C:22]2[C:23]([F:28])=[N:24][CH:25]=[CH:26][CH:27]=2)=[CH:11][CH:12]=3)[N:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:35](I)[C:36]([CH3:39])([CH3:38])[CH3:37]>CN(C=O)C.CC1OCCC1>[F:28][C:23]1[C:22]([C:10]2[CH:9]=[C:8]3[C@:4]4([N:3]=[C:2]([NH2:1])[CH2:7][O:6][CH2:5]4)[C:20]4[C:15](=[N:16][CH:17]=[C:18]([O:21][CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH:19]=4)[O:14][C:13]3=[CH:12][CH:11]=2)=[CH:27][CH:26]=[CH:25][N:24]=1
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참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 84953Propane, 1-iodo-2,2-dimethyl-HCID 67437546(S)-5'-amino-7-(2-fluoropyridin-3-yl)-2',6'-dihydrospiro[chromeno[2,3-b]pyridine-5,3'-[1,4]oxazin]-3-ol

생성물 1

HCID 58465959(S)-7-(2-fluoropyridin-3-yl)-3-(neopentyloxy)-2',6'-dihydrospiro[chromeno[2,3-b]pyridine-5,3'-[1,4]oxazin]-5'-amine수율 15.9%

시약·촉매·용매 2

HCID 6228
Dimethylformamide
용매
HCID 73012-Methyltetrahydrofuran용매

실험 절차

A solution of (S)-5′-amino-7-(2-fluoropyridin-3-yl)-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-3-ol (0.133 g, 0.352 mmol), potassium carbonate (0.194 g, 1.406 mmol), and neopentyl iodide (0.093 mL, 0.703 mmol) in 1.5 mL DMF was heated to 115° C. overnight. The reaction mixture was then diluted with 2-MeTHF and washed with water. The organics were dried over MgSO4 and concentrated. Purification of the crude residue by column chromatography [0-100% (9:1 EtOAc/MeOH)/DCM] gave (S)-7-(2-fluoropyridin-3-yl)-3-(neopentyloxy)-2′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.025 g, 0.056 mmol, 15.86% yield). MS m/z=449.20 [M+H]+. Calculated for C25H25FN4O3: 448.49.

후처리

  1. washwashed with water
  2. dry with materialThe organics were dried over MgSO4
  3. concentrationconcentrated
  4. customPurification of the crude residue by column chromatography [0-100% (9:1 EtOAc/MeOH)/DCM]

출처 및 근거

ORD 기록
ord-fdb75a400c1e4a059747c3beefce0dbc
출처 데이터셋
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08497264B2

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