Lithium Hydroxide → 4-((S)-8-(3-(((S)-2-(4-((S)-2-((S)-2-amino-3-methylbutanamido)propanamido)phenyl)-7-methoxy-5-oxo-5,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yl)oxy)propoxy)-7-methoxy-5-oxo-5,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-2-yl)benzoic acid

HRID 1050882Notes

Reaction equation

HRID 1050882 reaction equation
[NH2:1][C@@H:2]([CH:66]([CH3:68])[CH3:67])[C:3]([NH:5][C@@H:6]([CH3:65])[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH2:17][C@H:18]3[CH:24]=[N:23][C:22]4[CH:25]=[C:26]([O:31][CH2:32][CH2:33][CH2:34][O:35][C:36]5[C:37]([O:61][CH3:62])=[CH:38][C:39]6[C:45](=[O:46])[N:44]7[CH:47]=[C:48]([C:50]8[CH:59]=[CH:58][C:53]([C:54]([O:56]C)=[O:55])=[CH:52][CH:51]=8)[CH2:49][C@H:43]7[CH:42]=[N:41][C:40]=6[CH:60]=5)[C:27]([O:29][CH3:30])=[CH:28][C:21]=4[C:20](=[O:63])[N:19]3[CH:64]=2)=[CH:12][CH:11]=1)=[O:8])=[O:4].[OH-].[Li+]>C1COCC1.CO>[NH2:1][C@@H:2]([CH:66]([CH3:68])[CH3:67])[C:3]([NH:5][C@@H:6]([CH3:65])[C:7]([NH:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2[CH2:17][C@H:18]3[CH:24]=[N:23][C:22]4[CH:25]=[C:26]([O:31][CH2:32][CH2:33][CH2:34][O:35][C:36]5[C:37]([O:61][CH3:62])=[CH:38][C:39]6[C:45](=[O:46])[N:44]7[CH:47]=[C:48]([C:50]8[CH:51]=[CH:52][C:53]([C:54]([OH:56])=[O:55])=[CH:58][CH:59]=8)[CH2:49][C@H:43]7[CH:42]=[N:41][C:40]=6[CH:60]=5)[C:27]([O:29][CH3:30])=[CH:28][C:21]=4[C:20](=[O:63])[N:19]3[CH:64]=2)=[CH:14][CH:15]=1)=[O:8])=[O:4]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 117629188HCID 117629188, compound

Product 1

HCID 1176289634-((S)-8-(3-(((S)-2-(4-((S)-2-((S)-2-amino-3-methylbutanamido)propanamido)phenyl)-7-methoxy-5-oxo-5,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yl)oxy)propoxy)-7-methoxy-5-oxo-5,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-2-yl)benzoic acid

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To 9 (20 mg) in THF/CH3OH (2 mL) was added a lithium hydroxide solution (1 mL of a 0.1 M solution). The reaction mixture was stirred at an ambient temperature. At 5 hours, LC-MS revealed approximately a 30% conversion to desired product with significant decomposition. The reaction mixture was cooled to −80° C. for 16 hours. LC-MS showed a ˜1:1 mixture of 10 and 9. The reaction mixture was neutralized with 0.1N HCl (˜1 mL) and was concentrated to approximately 1 mL. DMSO (1 mL) and CH3CN (1 mL) were added, and the mixture was purified by preparatory reverse-phase HPLC. Product containing fractions were combined, frozen and lyophilized. This resulted in 1.7 mg (9%) of 10 as a yellow film: MS (ES+) m/z 938 [M+H]+.

Sources & evidence

ORD record
ord-9d4d8b4d1e3f428aa91bc90e31b1e8f0
Source dataset
uspto-grants-2016_07
Patent number
US09387259B2

Reaction notes

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