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 335926ノート

反応式

HRID 335926 の反応式
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

参加物

6

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

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

後処理

  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

出典と根拠

ORDレコード
ord-0f72b9cbaaa14bceb5fb12eceaf0ef94
出典データセット
uspto-grants-2014_11
特許番号
US08883782B2

反応ノート

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