Acetonitrile → Methyl 3-amino-6-[4-[(1-tert-butoxycarbonyl-3-piperidyl)sulfonyl]phenyl]pyrazine-2-carboxylate

HRID 78722노트

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HRID 78722 반응식
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([S:15]([CH:18]3[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19]3)(=[O:17])=[O:16])=[CH:11][CH:10]=2)O1.[NH2:32][C:33]1[C:34]([C:40]([O:42][CH3:43])=[O:41])=[N:35][C:36](Br)=[CH:37][N:38]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC#N>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.CCOCC.O>[NH2:32][C:33]1[C:34]([C:40]([O:42][CH3:43])=[O:41])=[N:35][C:36]([C:9]2[CH:14]=[CH:13][C:12]([S:15]([CH:18]3[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:29])([CH3:30])[CH3:28])=[O:25])[CH2:19]3)(=[O:17])=[O:16])=[CH:11][CH:10]=2)=[CH:37][N:38]=1

참가 물질

8

반응물 4

HCID 6342AcetonitrileHCID 62657Potassium Phosphate, TribasicHCID 227251Methyl 3-Amino-6-bromopyrazine-2-carboxylateHCID 86682773Tert-butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonylpiperidine-1-carboxylate

생성물 1

HCID 86682779Methyl 3-amino-6-[4-[(1-tert-butoxycarbonyl-3-piperidyl)sulfonyl]phenyl]pyrazine-2-carboxylate수율 90.02%

시약·촉매·용매 3

HCID 178418851HCID 178418851, 화합물촉매HCID 962Water용매HCID 3283Diethyl Ether용매

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온도
60 °C

실험 절차

tert-butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonylpiperidine-1-carboxylate (2 g, 4.431 mmol), methyl 3-amino-6-bromo-pyrazine-2-carboxylate (934.6 mg, 4.028 mmol) and K3PO4 (1.710 g, 8.056 mmol) with MeCN (14.09 mL)/water (3.133 mL). Degassed with vacuum/nitrogen over 5 cycles, treated with Pd[P(tBu)3]2 (114.9 mg, 0.2248 mmol), degassed further 5 cycles and stirred under nitrogen for 2 hours at 60° C. The reaction mixture was cooled to ambient temperature and poured onto icewater/ethylacetate. The organic layer was washed with aq NaHCO3, brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel eluting with 50-70% EtAc/petrol. The relevant fractions were concentrated in vacuo to a solid. Trituration with ether/petroleumether gave methyl 3-amino-6-[4-[(1-tert-butoxycarbonyl-3-piperidyl)sulfonyl]phenyl]pyrazine-2-carboxylate as a colourless solid (1.728 g, 3.626 mmol, 90.02%). H NMR (400.0 MHz, DMSO-d6) δ 9.05 (s, 1H), 8.3 (d, 2H), 8.0 (d, 2H), 7.7 (br s, 2H), 4.0-4.1 (m, 1H), 3.9 (s, 3H), 3.7-3.8 (m, 1H), 3.3-3.4 (m, 1H), 2.77-2.95 (m, 2H), 1.95-2.05 (m, 1H), 1.7-1.75 (m, 1H), 1.6-1.65 (m, 1H) and 1.20-1.40 (m, 10H) ppm; LC/MS m/z 421.1 [M−56+1]+.

후처리

  1. customDegassed with vacuum/nitrogen over 5 cycles
  2. customdegassed further 5 cycles
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. additionpoured onto icewater/ethylacetate
  5. washThe organic layer was washed with aq NaHCO3, brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by chromatography on silica gel eluting with 50-70% EtAc/petrol
  9. concentrationThe relevant fractions were concentrated in vacuo to a solid

출처 및 근거

ORD 기록
ord-80279b29d0df4b31a4b0a0e8fe3b9597
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08841449B2

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