4-Nitrobenzoic Acid → HCID 178464930, compound

HRID 246000Notes

Reaction equation

HRID 246000 reaction equation
[OH:1][C@@H:2]1[CH2:5][C@H:4]([CH:6]([NH:8][C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:20]4[C:28]5[C:23](=[CH:24][C:25]([F:29])=[CH:26][CH:27]=5)[N:22]([CH3:30])[N:21]=4)[N:18]=3)[N:13]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:12]=2)=[O:10])[CH3:7])[CH2:3]1.[N+:39]([C:42]1[CH:50]=[CH:49][C:45]([C:46](O)=[O:47])=[CH:44][CH:43]=1)([O-:41])=[O:40].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1.C(Cl)Cl>[F:29][C:25]1[CH:24]=[C:23]2[C:28]([C:20]([C:17]3[N:18]=[C:19]4[C:11]([C:9]([NH:8][CH:6]([C@H:4]5[CH2:3][C@H:2]([O:1][C:46](=[O:47])[C:45]6[CH:44]=[CH:43][C:42]([N+:39]([O-:41])=[O:40])=[CH:50][CH:49]=6)[CH2:5]5)[CH3:7])=[O:10])=[CH:12][N:13]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:37])([CH3:36])[CH3:38])[C:14]4=[N:15][CH:16]=3)=[N:21][N:22]2[CH3:30])=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 61084-Nitrobenzoic AcidHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 178464928HCID 178464928, compound

Product 1

HCID 178464930HCID 178464930, compoundYield 98.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(cis-3-hydroxy-cyclobutyl)-ethyl]-amide (200 mg, 0.37 mmol) in THF (4 mL) was added 4-nitrobenzoic acid (124 mg, 0.74 mmol) and triphenylphosphine (204 mg, 0.78 mmol). Then the reaction mixture was cooled to 0° C. and diethyl azodicarboxylate (123 μL, 0.78 mmol) was added dropwise. The reaction was stirred at room temperature overnight then diluted with CH2Cl2 (25 mL) and washed with 1.0 M aqueous NaOH. The aqueous phase was back-extracted with CH2Cl2 then the combined organics were dried over MgSO4 and concentrated. The residue was absorbed onto SiO2 and purified via chromatography with 20% to 80% EtOAc/hexanes to provide 250 mg (98%) of 4-nitrobenzoic acid trans-3-(1-{[2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-ethyl)-cyclobutyl ester as a white solid.

Workup

  1. washwashed with 1.0 M aqueous NaOH
  2. extractionThe aqueous phase was back-extracted with CH2Cl2
  3. dry with materialthe combined organics were dried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was absorbed onto SiO2
  6. custompurified via chromatography with 20% to 80% EtOAc/hexanes

Sources & evidence

ORD record
ord-d9e1549dbc844a2bb2f0b4465a56eebb
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…