Potassium Carbonate → 1,1-Dimethylethyl N-[1-(6-chloro-2-pyrazinyl)-4-piperidinyl]carbamate

HRID 1529255노트

반응식

HRID 1529255 반응식
Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([Cl:8])[N:3]=1.[CH3:9][C:10]([O:13][C:14]([NH:16][CH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)=[O:15])([CH3:12])[CH3:11].C([O-])([O-])=O.[K+].[K+].C[Sn](C)(C)C1N=C(N2CCC(NC(=O)OC(C)(C)C)CC2)C=NC=1>CN(C=O)C>[Cl:8][C:4]1[N:3]=[C:2]([N:20]2[CH2:19][CH2:18][CH:17]([NH:16][C:14](=[O:15])[O:13][C:10]([CH3:11])([CH3:9])[CH3:12])[CH2:22][CH2:21]2)[CH:7]=[N:6][CH:5]=1

참가 물질

6

반응물 4

HCID 11430Potassium CarbonateHCID 785042,6-DichloropyrazineHCID 7238334-(N-Boc-amino)piperidineHCID 67958144HCID 67958144, 화합물

생성물 1

HCID 534860761,1-Dimethylethyl N-[1-(6-chloro-2-pyrazinyl)-4-piperidinyl]carbamate수율 98%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
85 °C

실험 절차

A suspension of 2,6-dichloropyrazine (223.5 g, 1.5 mol, 1.0 eq), 4-N-boc-aminopiperidine (300 g, 1.5 mol, 1.0 eq) and K2CO3 (228 g, 1.65 mol, 1.1 eq) in DMF (900 mL) was heated to 85° C. for 20 h. LC-MS analysis showed that tert-butyl 1-(6-(trimethylstannyl)pyrazin-2-yl)piperidin-4-ylcarbamate was formed as the major product. The reaction mixture was cooled to RT and poured into ice-water (3 L). The resulting precipitate was collected by filtration, washed with water (1 L×2) and hexane (1 L×2), and dried at 50° C. under vacuum affording tert-butyl 1-(6-chloropyrazin-2-yl)piperidin-4-ylcarbamate (252 g, >98% purity) in 54% yield. MS (ESI, pos. ion) m/z: 393.0 (M+1). A suspension of tert-butyl 1-(6-chloropyrazin-2-yl)piperidin-4-ylcarbamate (245 g, 0.75 mol, 1.0 eq), hexamethylditin (492 g, 1.5 mol, 2.0 eq) and Pd(PPh3)4 (87 g, 0.075 mol, 0.1 eq) in anhydrous toluene (2 L) was degassed with N2 for 30 min and heated to 110° C. for 24 h. LC-MS analysis showed around 50% conversion and no more further reaction. The reaction mixture was cooled to RT, quenched with water (2 L), and stirred well. After filtration through a celite pad and phase separation, the aqueous layer was extracted with EtOAc (1 L×2). The combined organics were washed with brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography eluting with DCM/EtOAc (20/1), affording title compound 1d (150 g, >96% purity) in 45% yield. MS (ESI, pos. ion) m/z: 443.2 (M+1)

후처리

  1. customwas formed as the major product
  2. temperatureThe reaction mixture was cooled to RT
  3. filtrationThe resulting precipitate was collected by filtration
  4. washwashed with water (1 L×2) and hexane (1 L×2)
  5. customdried at 50° C. under vacuum

출처 및 근거

ORD 기록
ord-250dfd14e00a48afa2e23b77c1e68957
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09090593B2

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