Lithium triethylborohydride → (S)-2-(3-aminophenyl)-7-methoxy-8-(3-((S)-7-methoxy-2-(4-methoxyphenyl)-5-oxo-5,11a-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-8-yloxy)propyloxy)-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5(11aH)-one

HRID 594183Notes

Reaction equation

HRID 594183 reaction equation
[Li+].[B-](CC)(CC)CC.[NH2:9][C:10]1[CH:11]=[C:12]([C:16]2[CH2:17][C@@H:18]3[N:24]([CH:25]=2)[C:23](=[O:26])[C:22]2[CH:27]=[C:28]([O:70][CH3:71])[C:29]([O:31][CH2:32][CH2:33][CH2:34][O:35][C:36]4[C:67]([O:68][CH3:69])=[CH:66][C:39]5[C:40](=[O:65])[N:41]6[CH:56]=[C:55]([C:57]7[CH:62]=[CH:61][C:60]([O:63][CH3:64])=[CH:59][CH:58]=7)[CH2:54][C@H:42]6[C:43](=O)[N:44](COCC[Si](C)(C)C)[C:38]=5[CH:37]=4)=[CH:30][C:21]=2[N:20](COCC[Si](C)(C)C)[C:19]3=O)[CH:13]=[CH:14][CH:15]=1>C1COCC1.O>[NH2:9][C:10]1[CH:11]=[C:12]([C:16]2[CH2:17][C@@H:18]3[N:24]([CH:25]=2)[C:23](=[O:26])[C:22]2[CH:27]=[C:28]([O:70][CH3:71])[C:29]([O:31][CH2:32][CH2:33][CH2:34][O:35][C:36]4[C:67]([O:68][CH3:69])=[CH:66][C:39]5[C:40](=[O:65])[N:41]6[CH:56]=[C:55]([C:57]7[CH:62]=[CH:61][C:60]([O:63][CH3:64])=[CH:59][CH:58]=7)[CH2:54][C@H:42]6[CH:43]=[N:44][C:38]=5[CH:37]=4)=[CH:30][C:21]=2[N:20]=[CH:19]3)[CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 2

HCID 23712863Lithium triethylborohydride2×HCID 86676187(S)-2-(3-aminophenyl)-7-methoxy-8-(3-((S)-7-methoxy-2-(4-methoxyphenyl)-5,11-dioxo-10-((2-(trimethylsilyl)ethoxy)methyl)-5,10,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-8-yloxy)propyloxy)-10((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione

Product 1

HCID 45376562(S)-2-(3-aminophenyl)-7-methoxy-8-(3-((S)-7-methoxy-2-(4-methoxyphenyl)-5-oxo-5,11a-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-8-yloxy)propyloxy)-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5(11aH)-oneYield 77.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of superhydride (0.56 mL, 0.56 mmol, 1.0 M in THF) was added dropwise to a solution of the SEM dilactam (18) (0.271 g, 0.27 mmol) in dry THF (10 mL) at −78° C. under a nitrogen atmosphere. After 1 hr a further aliquot of superhydride solution (0.13 ml, 0.13 mmol) was added and the reaction mixture was allowed to stir for another 0.5 hr, at which time LC-MS indicated that reduction was complete. The reaction mixture was diluted with water and allowed to warm to room temperature. The reaction mixture was partitioned between chloroform and water, the layers were separated and the aqueous layer extracted with additional chloroform (emulsions). Finally the combined organic phase was washed with brine and dried over magnesium sulphate. The reduced product was dissolved in methanol, chloroform and water and allowed to stir in the presence of silica gel for 72 hours The crude product was subjected to flash column chromatography (methanol/chloroform gradient) to afford the desired imine product (150 mg, 0.21 mmol, 77%) after removal of excess eluent from selected fractions.

Workup

  1. customThe reaction mixture was partitioned between chloroform and water
  2. customthe layers were separated
  3. extractionthe aqueous layer extracted with additional chloroform (emulsions)
  4. washFinally the combined organic phase was washed with brine
  5. dry with materialdried over magnesium sulphate
  6. dissolutionThe reduced product was dissolved in methanol
  7. stirringto stir in the presence of silica gel for 72 hours The crude product

Sources & evidence

ORD record
ord-7ca6e9098bdf494899deb8f6e2739adc
Source dataset
uspto-grants-2016_01
Patent number
US09242013B2

Reaction notes

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