Water → HCID 131730692, compound

HRID 446643Notes

Reaction equation

HRID 446643 reaction equation
[OH-].[Li+].O.[CH:4](=[C:6]1[CH2:15][N:14]2[C@H:8]([CH:9]=[N:10][C:11]3[CH:20]=[C:19]([O:21][CH2:22][C:23]4[CH:28]=[C:27]([O:29][CH2:30][CH2:31][N:32]([CH3:60])[CH2:33][C:34]([S:37][CH2:38][C:39]([NH:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][O:47][CH2:48][CH2:49][O:50][CH2:51][CH2:52][O:53][CH2:54][CH2:55][C:56]([O:58]C)=[O:57])=[O:40])([CH3:36])[CH3:35])[CH:26]=[C:25]([CH2:61][O:62][C:63]5[C:79]([O:80][CH3:81])=[CH:78][C:66]6[C:67](=[O:77])[N:68]7[CH2:74][C:73](=[CH:75][CH3:76])[CH2:72][C@H:69]7[CH:70]=[N:71][C:65]=6[CH:64]=5)[N:24]=4)[C:18]([O:82][CH3:83])=[CH:17][C:12]=3[C:13]2=[O:16])[CH2:7]1)[CH3:5].P([O-])([O-])([O-])=O>C1COCC1.C(Cl)Cl>[CH:75](=[C:73]1[CH2:74][N:68]2[C@H:69]([CH:70]=[N:71][C:65]3[CH:64]=[C:63]([O:62][CH2:61][C:25]4[CH:26]=[C:27]([O:29][CH2:30][CH2:31][N:32]([CH3:60])[CH2:33][C:34]([S:37][CH2:38][C:39]([NH:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][O:47][CH2:48][CH2:49][O:50][CH2:51][CH2:52][O:53][CH2:54][CH2:55][C:56]([OH:58])=[O:57])=[O:40])([CH3:35])[CH3:36])[CH:28]=[C:23]([CH2:22][O:21][C:19]5[C:18]([O:82][CH3:83])=[CH:17][C:12]6[C:13](=[O:16])[N:14]7[CH2:15][C:6](=[CH:4][CH3:5])[CH2:7][C@H:8]7[CH:9]=[N:10][C:11]=6[CH:20]=5)[N:24]=4)[C:79]([O:80][CH3:81])=[CH:78][C:66]=3[C:67]2=[O:77])[CH2:72]1)[CH3:76]

Participants

7

Reactant 4

HCID 962WaterHCID 1061PhosphateHCID 3939Lithium HydroxideHCID 131730693HCID 131730693, compound

Product 1

HCID 131730692HCID 131730692, compoundYield 64.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

17.5 μl of an aqueous lithium hydroxide solution and 100 μl of water are added to 18 mg of methyl 3-{2-[2-(2-{2-[2-(2-([2-(2,6-bis[(S)-2-eth-(E)-ylidene-7-methoxy-1,2,3,11a-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-5-one-8-yloxymethyl]pyridin-4-yloxy)ethyl](methyl)amino}-1,1-dimethylethylsulphanyl)acetylamino]ethoxy}ethoxy)ethoxy]ethoxy}propanoate in solution in 270 μl of THF. After 2 h, the mixture is diluted in DCM and a phosphate buffer is added to pH=3. The resulting aqueous phase is extracted 3× with DCM, the combined organic phases are dried over MgSO4 and concentrated under RP and the residue is purified by flash chromatography on silica (Interchrom Puriflash Silica 15/35U 2G) using a gradient from 3 to 15% of methanol in DCM. 11.5 mg of 3-{2-[2-(2-{2-[2-(2-{[2-(2,6-bis[(S)-2-eth-(E)-ylidene-7-methoxy-1,2,3,11a-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-5-one-8-yloxymethyl]pyridin-4-yloxy)ethyl](methyl)amino}-1,1-dimethylethylsulphanyl)acetylamino]ethoxy}-ethoxy)ethoxy]ethoxy}propanoic acid are thus obtained. LC/MS (D): rt=0.88 min; [M+H2O+Na]+: m/z 1154; [M+H2O+H]+: m/z 1133; [M+H]+: m/z 1115.

Workup

  1. extractionThe resulting aqueous phase is extracted 3× with DCM
  2. dry with materialthe combined organic phases are dried over MgSO4
  3. concentrationconcentrated under RP
  4. customthe residue is purified by flash chromatography on silica (Interchrom Puriflash Silica 15/35U 2G)

Sources & evidence

ORD record
ord-596145cfbbbe400c8de9d1758115fa32
Source dataset
uspto-grants-2013_07
Patent number
US08481042B2

Reaction notes

Loading…