Aniline → HCID 118354000, compound

HRID 525301Notes

Reaction equation

HRID 525301 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:41])[C@@H:9]([CH3:40])[C:10]([NH:12][C@@H:13]([CH:37]([CH3:39])[CH3:38])[C:14]([N:16]1[C:20]2=[N:21][CH:22]=[CH:23][CH:24]=[C:19]2[CH2:18][C@H:17]1[CH2:25]OS(C1C=CC(C)=CC=1)(=O)=O)=[O:15])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[NH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>O1CCOCC1.C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[N:8]([CH3:41])[C@H:9]([C:10](=[O:11])[NH:12][C@H:13]([C:14]([N:16]1[C:20]2=[N:21][CH:22]=[CH:23][CH:24]=[C:19]2[CH2:18][C@H:17]1[CH2:25][NH:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:15])[CH:37]([CH3:39])[CH3:38])[CH3:40])([CH3:3])([CH3:2])[CH3:4]

Participants

6

Reactant 3

HCID 6115AnilineHCID 11430Potassium CarbonateHCID 131735585HCID 131735585, compound2×

Product 1

HCID 118354000HCID 118354000, compoundYield 69.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To the stirred solution of toluene-4-sulfonic acid (S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyryl}-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-2-ylmethyl ester (Intermediate 2) (50 mg, 0.085 mmol) in 1,4-dioxane (0.5 mL), K2CO3 (29.3 mg, 0.127 mmol), was added aniline (0.012 mL, 0.127 mmol) and the reaction mixture irradiated in a microwave at 125° C. for 1 h. The reaction mixture was diluted with DCM (10 mL), washed with water and brine and the separated organic layer was concentrated in vacuo. The crude product was purified by preparative HPLC (X Bridge Prep C18 (250×19.0 mm) 5μ, acetonitrile and 0.05% formic acid) to give methyl-{(S)-1-[(S)-2-methyl-1-((S)-2-phenylaminomethyl-2,3-dihydro-pyrrolo[2,3-b]pyridine-1-carbonyl)-propylcarbamoyl]-ethyl}-carbamic acid tert-butyl ester (30 mg), m/z=510.6 (M+H).

Workup

  1. customthe reaction mixture irradiated in a microwave at 125° C. for 1 h
  2. washwashed with water and brine
  3. concentrationthe separated organic layer was concentrated in vacuo
  4. customThe crude product was purified by preparative HPLC (X Bridge Prep C18 (250×19.0 mm) 5μ, acetonitrile and 0.05% formic acid)

Sources & evidence

ORD record
ord-fbed153a66c145888be15a55d2a50f5d
Source dataset
uspto-grants-2016_05
Patent number
US09340573B2

Reaction notes

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