Ammonia → 3-Aminomethyl-6-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridine

HRID 1191091노트

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HRID 1191091 반응식
[CH:1]1([CH2:4][NH:5][C:6]2[S:7][CH:8]=[C:9]([C:11]3[CH:18]=[CH:17][C:14]([C:15]#[N:16])=[CH:13][N:12]=3)[N:10]=2)[CH2:3][CH2:2]1.N.[H][H]>[Ni].CO>[NH2:16][CH2:15][C:14]1[CH:13]=[N:12][C:11]([C:9]2[N:10]=[C:6]([NH:5][CH2:4][CH:1]3[CH2:3][CH2:2]3)[S:7][CH:8]=2)=[CH:18][CH:17]=1

참가 물질

6

반응물 3

HCID 222AmmoniaHCID 59828824HCID 59828824, 화합물HCID 178418361HCID 178418361, 화합물

생성물 1

HCID 598288833-Aminomethyl-6-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridine수율 51.7%

시약·촉매·용매 2

HCID 935Nickel촉매HCID 887Methanol용매

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온도
40 °C

실험 절차

Add 6-[2-(cyclopropylmethylamino)-thiazol-4-yl]-nicotinonitrile (2.0 g, 7.8 mmol), Raney Nickel (2.0 mL), and 2M ammonia in methanol (200 mL) to a pressure vessel under a nitrogen atmosphere. Pressurize the vessel to 60 psi with hydrogen, and stir the mixture for 6 h at 40° C. Filter the mixture through Celite® and concentrate in vacuo to an oil. Dissolve the oil in EtOAc (300 mL) and saturated ammonium hydroxide (50 mL). Stir the solution for 20 h in a sealed flask at room temperature. Collect the organic layer and concentrate in vacuo. Purify the crude mixture by SCX chromatography followed by chromatography on silica gel (150 g) eluting with DCM/2M ammonia in methanol (99:1 to 85:15 gradient) to obtain the title compound (1.05 g, 51%). MS (ES+) m/z: 261 (M+H)+.

후처리

  1. filtrationFilter the mixture through Celite®
  2. concentrationconcentrate in vacuo to an oil
  3. dissolutionDissolve the oil in EtOAc (300 mL)
  4. stirringStir the solution for 20 h in a sealed flask at room temperature
  5. customCollect the organic layer
  6. concentrationconcentrate in vacuo
  7. customPurify the crude mixture by SCX chromatography
  8. washeluting with DCM/2M ammonia in methanol (99:1 to 85:15 gradient)

출처 및 근거

ORD 기록
ord-419a6b6d4fbd471097ca9e1e8522e50f
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08680091B2

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