1,2-Dichloroethane → (3R)-ethyl 3-(2-(1-(bis(tert-butoxycarbonyl)amino)isoquinolin-6-ylamino)-2-(4-(2-hydroxyethyl)-3,5-dimethylphenyl)acetamido)-3-(3-nitrophenyl)propanoate

HRID 735627Notes

Reaction equation

HRID 735627 reaction equation
C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.Cl.[NH2:16][C@@H:17]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([N+:30]([O-:32])=[O:31])[CH:25]=1)[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20].[C:33]([O:37][C:38]([N:40]([C:67]([O:69][C:70]([CH3:73])([CH3:72])[CH3:71])=[O:68])[C:41]1[C:50]2[C:45](=[CH:46][C:47]([NH:51][CH:52]([C:56]3[CH:61]=[C:60]([CH3:62])[C:59]([CH2:63][CH2:64][OH:65])=[C:58]([CH3:66])[CH:57]=3)[C:53](O)=[O:54])=[CH:48][CH:49]=2)[CH:44]=[CH:43][N:42]=1)=[O:39])([CH3:36])([CH3:35])[CH3:34].C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O>[C:70]([O:69][C:67]([N:40]([C:38]([O:37][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:39])[C:41]1[C:50]2[C:45](=[CH:46][C:47]([NH:51][CH:52]([C:56]3[CH:57]=[C:58]([CH3:66])[C:59]([CH2:63][CH2:64][OH:65])=[C:60]([CH3:62])[CH:61]=3)[C:53]([NH:16][C@@H:17]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([N+:30]([O-:32])=[O:31])[CH:25]=3)[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])=[O:54])=[CH:48][CH:49]=2)[CH:44]=[CH:43][N:42]=1)=[O:68])([CH3:73])([CH3:72])[CH3:71]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 578427352-(1-(Bis(tert-butoxycarbonyl)amino)isoquinolin-6-ylamino)-2-(4-(2-hydroxyethyl)-3,5-dimethylphenyl)acetic acidHCID 86614936(r)-Ethyl 3-amino-3-(3-nitrophenyl)propanoate hydrochloride salt

Product 1

HCID 57842695(3R)-ethyl 3-(2-(1-(bis(tert-butoxycarbonyl)amino)isoquinolin-6-ylamino)-2-(4-(2-hydroxyethyl)-3,5-dimethylphenyl)acetamido)-3-(3-nitrophenyl)propanoateYield 83%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

EDC (187 mg, 0.97 mmol) and HOAt (132 mg, 0.97 mmol) were added to a solution of 39A (268 mg, 0.97 mmol) and 50C (500 mg, 0.89 mmol) in DMF (10 mL). Triethylamine (0.36 mL, 2.7 mmol) was added to the reaction mixture and it was stirred at 50° C. for 3 h. The reaction mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by flash chromatography (0% to 20% MeOH in CH2Cl2) to yield 50D (580 mg, 83%) as a yellow solid. MS (ESI) m/z 786.9 (M+H)+.

Workup

  1. washwashed with water and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash chromatography (0% to 20% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-35e8a02c882c49c29fd86023e0c32e7e
Source dataset
uspto-grants-2009_09
Patent number
US07592331B2

Reaction notes

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