Sodium Bicarbonate → tert-Butyl (S)-4-(5-(1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-1,4-diazepane-1-carboxylate

HRID 2205595ノート

反応式

HRID 2205595 の反応式
Br[C:2]1[CH:3]=[C:4]2[N:13]([CH3:14])[CH:12]=[CH:11][C:5]2=[N:6][C:7]=1[C@@H:8]([NH2:10])[CH3:9].[N:15]1([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:21][CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.CC([O-])(C)C.[K+].C([O-])(O)=O.[Na+]>CCOC(C)=O.O1CCOCC1>[NH2:10][C@H:8]([C:7]1[N:6]=[C:5]2[CH:11]=[CH:12][N:13]([CH3:14])[C:4]2=[CH:3][C:2]=1[N:18]1[CH2:19][CH2:20][CH2:21][N:15]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:16][CH2:17]1)[CH3:9]

参加物

7

反応物 4

HCID 516892Sodium BicarbonateHCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 23665647Potassium tert-butoxideHCID 86707977(S)-1-(6-Bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine

生成物 1

HCID 118214737tert-Butyl (S)-4-(5-(1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)-1,4-diazepane-1-carboxylate収率 34%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

To a 50 mL pear flask were added (S)-1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (153 mg, 0.602 mmol) and tert-butyl 1,4-diazepane-1-carboxylate (241 mg, 1.20 mmol). After evacuating the flask and flushing it with nitrogen, the flask was charged with dioxane (1.6 mL) and potassium 2-methylpropan-2-olate (1.0 M in THF) (1.32 mL, 1.32 mmol). The mixture was then heated to 90° C. for 1 hour. After cooling, the mixture was worked up with saturated NaHCO3 and EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by preparative HPLC (acid mode, 25-50% ACN/water gradient). The product-containing fractions were combined, neutralized with saturated NaHCO3, concentrated in vacuo to remove ACN, and then extracted with EtOAc. The organic layers were combined, dried over MgSO4, filtered, and concentrated in vacuo to give the title compound (76 mg, 34%). ESI-MS m/z [M+H]+ calc'd for C20H31N5O2, 374. found 374.

後処理

  1. customAfter evacuating the flask
  2. customflushing it with nitrogen
  3. temperatureAfter cooling
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by preparative HPLC (acid mode, 25-50% ACN/water gradient)
  8. concentrationconcentrated in vacuo
  9. customto remove ACN
  10. extractionextracted with EtOAc
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-5773969b58754bcf9fa9884783ed6905
出典データセット
uspto-grants-2016_06
特許番号
US09371321B2

反応ノート

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