Triethylamine → 5-cyclopropyl-N-(1-cyclopropyl-2-(5-methyl-1,2,4-oxadiazol-3-yl)propan-2-yl)-4-(1-fluoropropan-2-yloxy)picolinamide

HRID 1480343ノート

反応式

HRID 1480343 の反応式
[CH:1]1([C:4]2[C:5]([O:13][CH:14]([CH3:17])[CH2:15][F:16])=[CH:6][C:7]([C:10]([OH:12])=O)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.Cl.[CH:48]1([CH2:51][C:52]([C:55]2[N:59]=[C:58]([CH3:60])[O:57][N:56]=2)([NH2:54])[CH3:53])[CH2:50][CH2:49]1>CN(C=O)C.C(OCC)(=O)C>[CH:1]1([C:4]2[C:5]([O:13][CH:14]([CH3:17])[CH2:15][F:16])=[CH:6][C:7]([C:10]([NH:54][C:52]([C:55]3[N:59]=[C:58]([CH3:60])[O:57][N:56]=3)([CH3:53])[CH2:51][CH:48]3[CH2:49][CH2:50]3)=[O:12])=[N:8][CH:9]=2)[CH2:2][CH2:3]1

参加物

7

反応物 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 710877902-Cyclopropyl-1-methyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethylamine hydrochlorideHCID 902040445-Cyclopropyl-4-(1-fluoropropan-2-yloxy)picolinic acid

生成物 1

HCID 902036905-cyclopropyl-N-(1-cyclopropyl-2-(5-methyl-1,2,4-oxadiazol-3-yl)propan-2-yl)-4-(1-fluoropropan-2-yloxy)picolinamide

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 5-cyclopropyl-4-(1-fluoropropan-2-yloxy)picolinic acid (enantiomer A) (example 287e, 0.08 g, 334 μmol) in dry DMF (2 ml) was added TBTU (113 mg, 351 μmol) and triethylamine (102 mg, 140 μl, 1.00 mmol). The reaction was stirred at room temperature for 30 minutes followed by addition of 1-cyclopropyl-2-(5-methyl-1,2,4-oxadiazol-3-yl)propan-2-amine hydrochloride (example 66e, 72.8 mg, 334 μmol). The reaction was then stirred at room temperature overnight. The reaction was diluted with ethyl acetate and extracted with a 1M aqueous solution of sodium bicarbonate. The organic phase was collected and the aqueous phase was back-extracted with ethyl acetate. Combined organic phases were dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a gradient of heptane and ethyl acetate to give the a mixture of epimers. The epimers were then separated by preparative chiral HPLC (Chiralpak AD, isopropanol/heptane) and the title compound was the second epimer collected (23 mg, 17%); MS (ESI, m/z): 403.4 (M+H+).

後処理

  1. stirringThe reaction was then stirred at room temperature overnight
  2. extractionextracted with a 1M aqueous solution of sodium bicarbonate
  3. customThe organic phase was collected
  4. extractionthe aqueous phase was back-extracted with ethyl acetate
  5. dry with materialCombined organic phases were dried over sodium sulfate
  6. customevaporated down to dryness
  7. customThe crude material was purified by flash chromatography on silica eluting with a gradient of heptane and ethyl acetate
  8. customto give
  9. additionthe a mixture of epimers
  10. customThe epimers were then separated by preparative chiral HPLC (Chiralpak AD, isopropanol/heptane)
  11. customcollected (23 mg, 17%)

出典と根拠

ORDレコード
ord-5631a2cc35cd4bccb07eadb2feb1d057
出典データセット
uspto-grants-2016_08
特許番号
US09409866B2

反応ノート

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