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

HRID 78722Notes

Reaction equation

HRID 78722 reaction equation
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

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
60 °C

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-80279b29d0df4b31a4b0a0e8fe3b9597
Source dataset
uspto-grants-2014_09
Patent number
US08841449B2

Reaction notes

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