1,2-Dichloroethane → Benzyl(2-{[(3S)-3-{[(benzyloxy)carbonyl]amino}-6-({[(8S,11S,14S)-14-[(tert-butoxycarbonyl)amino]-11-{3-[(tert-butoxycarbonyl)amino]propyl}-9-ethyl-5,17-dihydroxy-10,13-dioxo-9,12-diazatricyclo[14.3.1.12,6]henicosa-1(20),2(21),3,5,16,18-hexaen-8-yl]carbonyl}amino)hexanoyl]-amino}ethyl)carbamate

HRID 269659Notes

Reaction equation

HRID 269659 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:27][C:26]2[CH:28]=[C:22]([CH:23]=[CH:24][C:25]=2[OH:29])[C:21]2=[CH:30][C:17](=[C:18]([OH:31])[CH:19]=[CH:20]2)[CH2:16][C@@H:15]([C:32](O)=[O:33])[N:14]([CH2:35][CH3:36])[C:13](=[O:37])[C@H:12]([CH2:38][CH2:39][CH2:40][NH:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[NH:11][C:10]1=[O:49])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.C([N:58]([C@H:62]([CH2:67][C:68]([NH:70][CH2:71][CH2:72][NH:73][C:74]([O:76][CH2:77][C:78]1[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=1)=[O:75])=[O:69])[CH2:63][CH2:64][CH2:65][NH2:66])[C:59](=[O:61])[OH:60])C1C=CC=CC=1.[CH2:84](Cl)CCl.[CH:88]1[CH:89]=[CH:90][C:91]2N(O)N=N[C:92]=2[CH:93]=1>CN(C)C=O>[CH2:77]([O:76][C:74](=[O:75])[NH:73][CH2:72][CH2:71][NH:70][C:68](=[O:69])[CH2:67][C@@H:62]([NH:58][C:59]([O:60][CH2:84][C:92]1[CH:91]=[CH:90][CH:89]=[CH:88][CH:93]=1)=[O:61])[CH2:63][CH2:64][CH2:65][NH:66][C:32]([C@H:15]1[N:14]([CH2:35][CH3:36])[C:13](=[O:37])[C@H:12]([CH2:38][CH2:39][CH2:40][NH:41][C:42]([O:44][C:45]([CH3:46])([CH3:48])[CH3:47])=[O:43])[NH:11][C:10](=[O:49])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:27][C:26]2[CH:28]=[C:22]([CH:23]=[CH:24][C:25]=2[OH:29])[C:21]2=[CH:30][C:17](=[C:18]([OH:31])[CH:19]=[CH:20]2)[CH2:16]1)=[O:33])[C:78]1[CH:79]=[CH:80][CH:81]=[CH:82][CH:83]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 66879719(8S,11S,14S)-14-[(tert-Butoxycarbonyl)amino]-11-{3-[(tert-butoxycarbonyl)amino]propyl}-9-ethyl-5,17-dihydroxy-10,13-dioxo-9,12-diazatricyclo[14.3.1.12,6]henicosa-1(20),2(21),3,5,16,18-hexaene-8-carboxylic acidHCID 69216382benzyl((1S)-4-amino-1-{2-[(2-{[(benzyloxy)carbonyl]amino}ethyl)amino]-2-oxoethyl}butyl)carbamate hydrochloride

Product 1

HCID 131727163Benzyl(2-{[(3S)-3-{[(benzyloxy)carbonyl]amino}-6-({[(8S,11S,14S)-14-[(tert-butoxycarbonyl)amino]-11-{3-[(tert-butoxycarbonyl)amino]propyl}-9-ethyl-5,17-dihydroxy-10,13-dioxo-9,12-diazatricyclo[14.3.1.12,6]henicosa-1(20),2(21),3,5,16,18-hexaen-8-yl]carbonyl}amino)hexanoyl]-amino}ethyl)carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Under argon, 30 mg (0.044 mmol) of (8S,11S,14S)-14-[(tert-butoxycarbonyl)amino]-11-{3-[(tert-butoxycarbonyl)amino]propyl}-9-ethyl-5,17-dihydroxy-10,13-dioxo-9,12-diazatricyclo-[14.3.1.12,6]henicosa-1(20),2(21),3,5,16,18-hexaene-8-carboxylic acid (Example 170A) and 80 mg (0.162 mmol) of benzyl-((1S)-4-amino-1-{2-[(2-{[(benzyloxy)carbonyl]amino}ethyl)amino]-2-oxoethyl}butyl)carbamate hydrochloride (Example 105A) are dissolved in 2 ml of dimethylformamide. Then, at 0° C. (ice bath), 31.16 mg (0.162 mmol) of EDC and 1.95 mg (0.014 mmol) of HOBt are added. The mixture is slowly warmed to RT and stirred at 50° C. for 3 days. The solution is concentrated in vacuo and the residue is purified by preparative HPLC.

Workup

  1. concentrationThe solution is concentrated in vacuo
  2. customthe residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-77ae29f870f642e184f8a0aedda7f971
Source dataset
uspto-grants-2008_11
Patent number
US07446102B2

Reaction notes

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