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

HRID 78722ノート

反応式

HRID 78722 の反応式
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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418851HCID 178418851、化合物触媒HCID 962Water溶媒HCID 3283Diethyl Ether溶媒

反応条件

温度
60 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-80279b29d0df4b31a4b0a0e8fe3b9597
出典データセット
uspto-grants-2014_09
特許番号
US08841449B2

反応ノート

読み込み中…