Triethylamine → tert-butyl N-tert-butoxycarbonyl-N-[3-[3-[4-(chloromethyl)phenyl]isoxazol-5-yl]-5-(4-isopropylsulfonylphenyl)pyrazin-2-yl]carbamate

HRID 81377Notes

Reaction equation

HRID 81377 reaction equation
C(N(CC)CC)C.[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:43][CH2:44][C:45]1[CH:54]=[CH:53][C:48]([C:49](Cl)=[N:50][OH:51])=[CH:47][CH:46]=1>C(Cl)Cl>[C:8]([O:12][C:13]([N:15]([C:23]1[C:28]([C:29]2[O:51][N:50]=[C:49]([C:48]3[CH:53]=[CH:54][C:45]([CH2:44][Cl:43])=[CH:46][CH:47]=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)[C:16](=[O:22])[O:17][C:18]([CH3:20])([CH3:21])[CH3:19])=[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 766866014-(Chloromethyl)-N-hydroxybenzimidoyl chloride

Product 1

HCID 86680730tert-butyl N-tert-butoxycarbonyl-N-[3-[3-[4-(chloromethyl)phenyl]isoxazol-5-yl]-5-(4-isopropylsulfonylphenyl)pyrazin-2-yl]carbamateYield 83.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethylamine (899.0 mg, 1.238 mL, 8.884 mmol) was added to a solution of tert-butyl N-tert-butoxycarbonyl-N-[3-ethynyl-5-(4-isopropylsulfonylphenyl)pyrazin-2-yl]carbamate 8 (4.05 g, 8.074 mmol) and 4-(chloromethyl)-N-hydroxy-benzimidoyl chloride (2.063 g, 8.494 mmol) in DCM (12 mL). The mixture was stirred at RT for 22 h then partitioned between DCM and an ice/water solution. The combined organic extract was dried over MgSO4 and concentrated under reduced pressure then purified by chromatography on silica gel (eluent 30-50% EtAc/petrol) yielding tert-butyl N-tert-butoxycarbonyl-N-[3-[3-[4-(chloromethyl)phenyl]isoxazol-5-yl]-5-(4-isopropylsulfonylphenyl)pyrazin-2-yl]carbamate as colourless crystals (4.53 g, 79%). 1H NMR (400 MHz, CDCl3) δ 1.41 (18H, s), 4.66 (2H, s), 7.37 (1H, s), 7.54 (2H, d, J=8.0 Hz), 7.90 (2H, d, J=8.0 Hz), 8.66 (1H, s)

Workup

  1. customthen partitioned between DCM
  2. extractionThe combined organic extract
  3. dry with materialwas dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customthen purified by chromatography on silica gel (eluent 30-50% EtAc/petrol)

Sources & evidence

ORD record
ord-8b02f920e68d4b1aa48d8956a4a23089
Source dataset
uspto-grants-2014_09
Patent number
US08846686B2

Reaction notes

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