1,2-Dichloroethane → 1-[4-(Thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-N-(N-methoxycarbonyl-(L)-valyl)amino-6-phenyl-2-azahexane

HRID 1873248Notes

Reaction equation

HRID 1873248 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:10]([OH:12])=O)[CH:7]([CH3:9])[CH3:8])=[O:4].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[S:27]1[C:31]([C:32]2[CH:37]=[CH:36][C:35]([CH2:38][N:39]([NH:52][C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:40][C@H:41]([OH:51])[C@@H:42]([NH2:50])[CH2:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[CH:34][CH:33]=2)=[CH:30][N:29]=[CH:28]1>CN(C=O)C>[S:27]1[C:31]([C:32]2[CH:37]=[CH:36][C:35]([CH2:38][N:39]([NH:52][C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:40][C@H:41]([OH:51])[C@@H:42]([NH:50][C:10](=[O:12])[C@H:6]([CH:7]([CH3:8])[CH3:9])[NH:5][C:3]([O:2][CH3:1])=[O:4])[CH2:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[CH:34][CH:33]=2)=[CH:30][N:29]=[CH:28]1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 107191051-[4-(Thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-amino-6-phenyl-2-azahexaneHCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acid

Product 1

HCID 108177421-[4-(Thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-N-(N-methoxycarbonyl-(L)-valyl)amino-6-phenyl-2-azahexane

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Under a nitrogen atmosphere, 2.66 g (15.2 mmol) of N-methoxycarbonyl-(L)-valine, 5.46 g (28.5 mmol) of EDC and 2.57 g (19 mmol) of HOBT are dissolved in 42 ml of DMF. 7.9 ml (57 mmol) of TEA are added and after 20 min a solution of 4.46 g (9.5 mmol) of 1-[4-(thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-(tert-butoxycarbonyl)amino-5(S)-amino-6-phenyl-2-azahexane (Example 2b) in 85 ml of DMF is added dropwise. After 1.5 hours, the reaction mixture is worked up analogously to Example 2c. Crystallisation from THF/ether yields the title compound: m.p: 114-115° C.; HPLC20-100 :tRet =15.1; FAB MS (M+H)+ =626.

Workup

  1. additionis added dropwise
  2. customCrystallisation from THF/ether

Sources & evidence

ORD record
ord-be99ef649a69479c8acfd09b291708c2
Source dataset
uspto-grants-2000_08
Patent number
US06110946

Reaction notes

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