Trifluoroacetic acid → Tert-butyl 5-[5-[3-[bis(tert-butoxycarbonyl)amino]-6-bromopyrazin-2-yl]isoxazol-3-yl]indole-1-carboxylate

HRID 331497

Reaction equation

HRID 331497 reaction equation
[OH:1][N:2]=[CH:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH:8]=[CH:7]2.[Br:20][C:21]1[N:22]=[C:23]([C:42]#[CH:43])[C:24]([N:27]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[N:25][CH:26]=1.C(OI(C1C=CC=CC=1)OC(=O)C)(=O)C.FC(F)(F)C(O)=O>CO>[C:38]([O:37][C:35]([N:27]([C:28]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:34])[C:24]1[C:23]([C:42]2[O:1][N:2]=[C:3]([C:4]3[CH:5]=[C:6]4[C:10](=[CH:11][CH:12]=3)[N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH:8]=[CH:7]4)[CH:43]=2)=[N:22][C:21]([Br:20])=[CH:26][N:25]=1)=[O:36])([CH3:41])([CH3:40])[CH3:39]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 76724Iodobenzene diacetateHCID 58070394tert-butyl N-(5-bromo-3-ethynylpyrazin-2-yl)-N-[(tert-butoxy)carbonyl]carbamateHCID 88996357HCID 88996357, compound

Product 1

HCID 89037198Tert-butyl 5-[5-[3-[bis(tert-butoxycarbonyl)amino]-6-bromopyrazin-2-yl]isoxazol-3-yl]indole-1-carboxylateYield 16.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of tert-butyl 5-((hydroxyimino)methyl)-1H-indole-1-carboxylate (260.3 mg, 1 mmol) in methanol (1 mL) was added slowly to a stirred solution of tert-butyl N-(5-bromo-3-ethynyl-pyrazin-2-yl)-N-tert-butoxycarbonyl-carbamate (438.1 mg, 1.100 mmol) and (diacetoxyiodo)benzene (354.3 mg, 1.100 mmol) in methanol (2 mL) containing trifluoroacetic acid (15 μL, 0.1947 mmol) at ambient temperature. The reaction was stirred at this temperature for 17 hours then concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion, 40 g column) loaded with dichloromethane and eluted with 0 to 50% ethyl acetate/petroleum ether. Product fractions were combined and concentrate in vacuo to give the sub-title product as a white solid (108 mg, 16% Yield). 1H NMR (400.0 MHz, DMSO-d6) δ 1.22 (s, 18H), 1.57 (s, 9H), 6.73 (d, 1H), 7.69 (d, 1H), 7.80 (s, 1H), 7.89 (dd, 1H), 8.11 (d, 1H), 8.23 (d, 1H) and 8.94 (s, 1H) ppm.

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe residue was purified by column chromatography (ISCO Companion, 40 g column)
  3. washeluted with 0 to 50% ethyl acetate/petroleum ether
  4. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-a68360ef282b44fe8b6fd13654043420
Source dataset
uspto-grants-2014_11
Patent number
US08877759B2

Linked notes

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