Dimethylformamide → 2-(1-(bis(tert-butoxycarbonyl)amino)isoquinolin-6-ylamino)-2-[4-(2-hydroxy-butyl)-phenyl]-N-(3-nitro-benzyl)-acetamide

HRID 735684Notes

Reaction equation

HRID 735684 reaction equation
[C:1]([O:5][C:6]([N:8]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C:9]1[C:18]2[C:13](=[CH:14][C:15]([NH:19][CH:20]([C:24]3[CH:29]=[CH:28][C:27]([CH2:30][CH:31]([OH:34])[CH2:32][CH3:33])=[CH:26][CH:25]=3)[C:21]([OH:23])=O)=[CH:16][CH:17]=2)[CH:12]=[CH:11][N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[C:43]([C:45]1[CH:46]=[C:47]([CH:50]=[CH:51][CH:52]=1)CN)#[N:44].C1CN([P+]([O:69][N:70]2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CN(C=[O:90])C>O>[C:1]([O:5][C:6]([N:8]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C:9]1[C:18]2[C:13](=[CH:14][C:15]([NH:19][CH:20]([C:24]3[CH:25]=[CH:26][C:27]([CH2:30][CH:31]([OH:34])[CH2:32][CH3:33])=[CH:28][CH:29]=3)[C:21]([NH:44][CH2:43][C:45]3[CH:52]=[CH:51][CH:50]=[C:47]([N+:70]([O-:69])=[O:90])[CH:46]=3)=[O:23])=[CH:16][CH:17]=2)[CH:12]=[CH:11][N:10]=1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 2724699PyBOPHCID 235092983-Cyanobenzylamine hydrochlorideHCID 578427622-(1-(Bis(tert-butoxycarbonyl)amino)isoquinolin-6-ylamino)-2-(4-(2-hydroxybutyl)phenyl)acetic acid

Product 1

HCID 578427912-(1-(bis(tert-butoxycarbonyl)amino)isoquinolin-6-ylamino)-2-[4-(2-hydroxy-butyl)-phenyl]-N-(3-nitro-benzyl)-acetamideYield 63%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

70E (140 mg, 0.25 mmol) was mixed with 3-cyanobenzylamine hydrochloride (57 mg, 0.3 mmol), PyBOP (156 mg, 0.3 mmol), TEA (76 mg, 0.75 mmol) in DMF (3 mL) and stirred at rt for 16 h. The mixture was diluted with H2O and extracted with EtOAc (3×20 mL). The organic layer washed with brine, dried (Na2SO4) and concentrated. Purification via flash chromatography (0-80% EtOAc/hexanes) afforded 70F (180 mg, 63%). MS (ESI) m/z 700.8 (M+H)+.

Workup

  1. extractionextracted with EtOAc (3×20 mL)
  2. washThe organic layer washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customPurification via flash chromatography (0-80% EtOAc/hexanes)

Sources & evidence

ORD record
ord-cc1b6631405446c79ac6214e7823512a
Source dataset
uspto-grants-2009_09
Patent number
US07592331B2

Reaction notes

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