Diisopropylethylamine → (S)-N-(2'-amino-3-(5,6-dihydro-2H-pyran-3-yl)-1-fluoro-5',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,4'-[1,3]oxazin]-7-yl)-5-chloropicolinamide

HRID 931646ノート

反応式

HRID 931646 の反応式
[O:1]1[CH2:6][CH2:5][CH:4]=[C:3]([C:7]2[N:12]=[C:11]([F:13])[C:10]3[O:14][C:15]4[C:20]([C@@:21]5([CH2:26][CH2:25][O:24][C:23]([NH2:27])=[N:22]5)[C:9]=3[CH:8]=2)=[CH:19][C:18]([NH2:28])=[CH:17][CH:16]=4)[CH2:2]1.[Cl:29][C:30]1[CH:31]=[CH:32][C:33]([C:36](O)=[O:37])=[N:34][CH:35]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:27][C:23]1[O:24][CH2:25][CH2:26][C@:21]2([C:9]3[CH:8]=[C:7]([C:3]4[CH2:2][O:1][CH2:6][CH2:5][CH:4]=4)[N:12]=[C:11]([F:13])[C:10]=3[O:14][C:15]3[C:20]2=[CH:19][C:18]([NH:28][C:36](=[O:37])[C:33]2[CH:32]=[CH:31][C:30]([Cl:29])=[CH:35][N:34]=2)=[CH:17][CH:16]=3)[N:22]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 27628725-Chloro-2-picolinic acidHCID 117600889(S)-3-(5,6-dihydro-2H-pyran-3-yl)-1-fluoro-5',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,4'-[1,3]oxazine]-2',7-diamine

生成物 1

HCID 71506897(S)-N-(2'-amino-3-(5,6-dihydro-2H-pyran-3-yl)-1-fluoro-5',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,4'-[1,3]oxazin]-7-yl)-5-chloropicolinamide収率 25.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of (S)-3-(5,6-dihydro-2H-pyran-3-yl)-1-fluoro-5′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazine]-2′,7-diamine (0.095 g, 0.248 mmol) in DMF (1 mL) were added 5-chloro-2-pyridinecarboxylic acid (0.043 g, 0.273 mmol), 0-(−7-azabenzotriazol-1-yl)-n,′n,′n,′n′-tetramethyluronium pf6 (0.099 g, 0.261 mmol) and Hunig's base (0.086 ml, 0.497 mmol) and the resulting mixture was stirred at rt for 15 h. The mixture was quenched with 5 drops of 2 N HCl and stirred for 1 min followed by the addition of water and extracted with EtOAc. The combined organics were dried over Na2SO4, filtered, concentrated and chromatographed on silica gel using 0-3% MeOH/DCM. The product was repurified by HPLC to afford (S)—N-(2′-amino-3-(5,6-dihydro-2H-pyran-3-yl)-1-fluoro-5′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazin]-7-yl)-5-chloropicolinamide as a white solid (0.0334 g, 0.064 mmol, 25.8% yield). MS m/z=522.0 [M+H]+.

後処理

  1. customThe mixture was quenched with 5 drops of 2 N HCl
  2. stirringstirred for 1 min
  3. additionfollowed by the addition of water
  4. extractionextracted with EtOAc
  5. dry with materialThe combined organics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customchromatographed on silica gel using 0-3% MeOH/DCM
  9. customThe product was repurified by HPLC

出典と根拠

ORDレコード
ord-7cfb41a02ea44ddd913fd5f678463c57
出典データセット
uspto-grants-2016_03
特許番号
US09296759B2

反応ノート

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