Triethylamine → HCID 86680659, compound

HRID 1615418Notes

Reaction equation

HRID 1615418 reaction equation
CCN(CC)CC.[C:8]([O:12][C:13]([N:15]([C:23]1[C:28]([C:29]#[CH:30])=[N:27][C:26]([C:31]2[CH:36]=[CH:35][C:34]([S:37]([CH:40]([CH3:42])[CH3:41])(=[O:39])=[O:38])=[CH:33][CH:32]=2)=[CH:25][N:24]=1)[C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:14])([CH3:11])([CH3:10])[CH3:9].Cl/[C:44](/[C:47]1[CH:52]=[CH:51][C:50]([C@@H:53]2[CH2:58][O:57][CH2:56][CH2:55][N:54]2[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])=[CH:49][CH:48]=1)=[N:45]\[OH:46]>C1COCC1>[C:8]([O:12][C:13]([N:15]([C:16]([O:17][C:18]([CH3:20])([CH3:21])[CH3:19])=[O:22])[C:23]1[C:28]([C:29]2[O:46][N:45]=[C:44]([C:47]3[CH:48]=[CH:49][C:50]([C@@H:53]4[CH2:58][O:57][CH2:56][CH2:55][N:54]4[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])=[CH:51][CH:52]=3)[CH:30]=2)=[N:27][C:26]([C:31]2[CH:32]=[CH:33][C:34]([S:37]([CH:40]([CH3:42])[CH3:41])(=[O:39])=[O:38])=[CH:35][CH:36]=2)=[CH:25][N:24]=1)=[O:14])([CH3:9])([CH3:10])[CH3:11]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 59471983N,N-Di(Boc)-3-ethynyl-5-[4-(isopropylsulfonyl)phenyl]pyrazin-2-amineHCID 141627790HCID 141627790, compound

Product 1

HCID 86680659HCID 86680659, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Et3N (54.34 mg, 74.85 μL, 0.5370 mmol) was added to a solution of tert-butyl N-tert-butoxycarbonyl-N-[3-ethynyl-5-(4-isopropylsulfonylphenyl)pyrazin-2-yl]carbamate 4 (224.5 mg, 0.4475 mmol) and tert-butyl (3R)-3-[4-[(Z)—C-chloro-N-hydroxy-carbonimidoyl]phenyl]morpholine-4-carboxylate 13 (183 mg, 0.5370 mmol) in THF (4 mL) and the resulting solution stirred at rt for 30 min and then heated at 65° C. for 2 h. The reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was purified by column chromatography on silica, using the ISCO column companion system, eluting with ethyl acetate/petroleum ether (0-50% EtOAc, 8 g column) Product began to elute at 33% EtOAc. Product fractions were combined and concentrated in vacuo to leave the product as a cream coloured solid (144 mg, 40% yield); 1.20 (6H, d), 1.30 (18H, s), 1.42 (9H, s), 3.07 (1H, m), 3.50-3.60 (3H, m), 3.73-3.85 (3H, m), 4.32 (1H, m), 5.06 (1H, s), 7.53 (2H, m), 8.07 (5H, m), 8.64 (2H, m) and 9.51 (1H, s) ppm

Workup

  1. temperatureheated at 65° C. for 2 h
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by column chromatography on silica
  5. washeluting with ethyl acetate/petroleum ether (0-50% EtOAc, 8 g column) Product
  6. washto elute at 33% EtOAc
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c5e40dc4cb284d89844582ae954129cf
Source dataset
uspto-grants-2014_07
Patent number
US08765751B2

Reaction notes

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