1,2-Dichloroethane → N-(tert-butoxycarbonyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-({[(2S)-1-(benzyloxy)-3-phenylpropan-2-yl]amino)}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

HRID 879241Notes

Reaction equation

HRID 879241 reaction equation
C(N(CC)C(C)C)(C)C.[CH:10]1[CH:11]=[CH:12][C:13]2N(O)N=N[C:14]=2[CH:15]=1.C(Cl)CCl.[C:24]([O:28][C:29]([N:31]([CH3:71])[C@H:32]([C:36]([NH:38][C@H:39]([C:43]([N:45]([C@@H:47]([C@@H:67]([CH3:70])[CH2:68][CH3:69])[C@H:48]([O:65][CH3:66])[CH2:49][C:50]([N:52]1[CH2:56][CH2:55][CH2:54][C@H:53]1[C@H:57]([O:63][CH3:64])[C@H:58]([C:60](O)=[O:61])[CH3:59])=[O:51])[CH3:46])=[O:44])[CH:40]([CH3:42])[CH3:41])=[O:37])[CH:33]([CH3:35])[CH3:34])=[O:30])([CH3:27])([CH3:26])[CH3:25].Cl.[CH2:73]([O:80][CH2:81][C@@H:82]([NH2:90])[CH2:83][C:84]1[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=1)C1C=CC=CC=1>CN(C=O)C>[C:24]([O:28][C:29]([N:31]([CH3:71])[C@H:32]([C:36]([NH:38][C@H:39]([C:43]([N:45]([C@@H:47]([C@@H:67]([CH3:70])[CH2:68][CH3:69])[C@H:48]([O:65][CH3:66])[CH2:49][C:50]([N:52]1[CH2:56][CH2:55][CH2:54][C@H:53]1[C@H:57]([O:63][CH3:64])[C@@H:58]([CH3:59])[C:60]([NH:90][C@@H:82]([CH2:83][C:84]1[CH:85]=[CH:86][CH:87]=[CH:88][CH:89]=1)[CH2:81][O:80][CH2:73][C:14]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:15]=1)=[O:61])=[O:51])[CH3:46])=[O:44])[CH:40]([CH3:42])[CH3:41])=[O:37])[CH:33]([CH3:34])[CH3:35])=[O:30])([CH3:25])([CH3:27])[CH3:26]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 12815229(1S)-1-Benzyl-2-(benzyloxy)ethylamine hydrochloride2×HCID 71294483Boc-NMeVal-Val-Dil-Dap2×

Product 1

HCID 86678347N-(tert-butoxycarbonyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-({[(2S)-1-(benzyloxy)-3-phenylpropan-2-yl]amino)}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

15.3 μl (88 μmol) of N,N-diisopropylethylamine, 6.7 mg (44 μmol) of HOBt, and 6.7 mg (35 μmol) of EDC were added to a solution of 20 mg (29 μmol) of N-(tert.-butoxycarbonyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-2-carboxy-1-methoxypropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide (intermediate 15) in 1 ml DMF and the composition was then stirred for 30 minutes. Then, 7.8 mg (32 μmol) of (2S)-1-(benzyloxy)-3-phenylpropane-2-amine-hydrochloride (intermediate 31) were added. After having stirred the reaction composition overnight, the components thereof where directly separated by means of preparative HPLC. The yield was 26 mg (98% o. th.) of the title compound.

Workup

  1. stirringAfter having stirred the reaction composition overnight
  2. customthe components thereof where directly separated by means of preparative HPLC

Sources & evidence

ORD record
ord-a4d67604295346a0bbcde344c3cb4aeb
Source dataset
uspto-grants-2015_03
Patent number
US08987209B2

Reaction notes

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