1,4-Dioxane → (S)-3-(6,6-dimethyl-3,6-dihydro-2H-pyran-4-yl)-7-(5-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-c]pyridine-5,4'-oxazol]-2'-amine

HRID 335926노트

반응식

HRID 335926 반응식
Cl[C:2]1[N:7]=[CH:6][C:5]2[O:8][C:9]3[C:14]([C@@:15]4([CH2:19][O:18][C:17]([NH2:20])=[N:16]4)[C:4]=2[CH:3]=1)=[CH:13][C:12]([C:21]1[CH:22]=[N:23][CH:24]=[C:25]([F:27])[CH:26]=1)=[CH:11][CH:10]=3.[CH3:28][C:29]1([CH3:44])[O:34][CH2:33][CH2:32][C:31](B2OC(C)(C)C(C)(C)O2)=[CH:30]1.O1CCOCC1>CCOC(C)=O.O>[CH3:28][C:29]1([CH3:44])[O:34][CH2:33][CH2:32][C:31]([C:2]2[N:7]=[CH:6][C:5]3[O:8][C:9]4[C:14]([C@@:15]5([CH2:19][O:18][C:17]([NH2:20])=[N:16]5)[C:4]=3[CH:3]=2)=[CH:13][C:12]([C:21]2[CH:22]=[N:23][CH:24]=[C:25]([F:27])[CH:26]=2)=[CH:11][CH:10]=4)=[CH:30]1

참가 물질

6

반응물 3

HCID 312751,4-DioxaneHCID 585467722-(6,6-dimethyl-3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86658490(S)-3-chloro-7-(5-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-c]pyridine-5,4'-oxazol]-2'-amine

생성물 1

HCID 53464570(S)-3-(6,6-dimethyl-3,6-dihydro-2H-pyran-4-yl)-7-(5-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-c]pyridine-5,4'-oxazol]-2'-amine

시약·촉매·용매 2

HCID 962Water용매2회HCID 8857Ethyl Acetate용매

실험 절차

A glass microwave reaction vessel was charged with (S)-3-chloro-7-(5-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-oxazol]-2′-amine (0.250 g, 0.653 mmol; prepared as described in Method BB41), 2-(6,6-dimethyl-3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.311 g, 1.306 mmol), bis(di-tert-butylphenylphosphine)dichloropalladium (II) (0.041 g, 0.065 mmol), dioxane (3 mL) and water (0.8 mL). The reaction mixture was exposed to MW radiation at 105° C. for 30 min in a microwave reactor. The mixture was diluted with EtOAc and water. The organic layer was washed with saturated sodium carbonate and dried over sodium sulfate. The crude material was initially purified by silica gel chromatography using 2-10% MeOH (2M NH3)-CH2Cl2) followed by further purification by SFC chromatography to give (S)-3-(6,6-dimethyl-3,6-dihydro-2H-pyran-4-yl)-7-(5-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-c]pyridine-5,4′-oxazol]-2′-amine

후처리

  1. customA glass microwave reaction vessel
  2. washThe organic layer was washed with saturated sodium carbonate
  3. dry with materialdried over sodium sulfate
  4. customThe crude material was initially purified by silica gel chromatography
  5. customfollowed by further purification by SFC chromatography

출처 및 근거

ORD 기록
ord-0f72b9cbaaa14bceb5fb12eceaf0ef94
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08883782B2

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