Sodium Carbonate → (S)-2-(2-aminophenyl)-7-methoxy-8-(3-(((S)-7-methoxy-2-(4-methoxyphenyl)-5,11-dioxo-10((2-(trimethylsilyl)ethoxy)methyl)-5,10,11,11a-tetrahydro-pyrrolo[2,1-c][1,4]benzodiazepin-8-yl)oxy)propoxy)-10-((2-(trimethylsilyl)ethoxy)methyl)-pyrrolo[2,1-c][1,4]-benzodiazepine-5,11(10H,11aH)-dione

HRID 594185Notes

Reaction equation

HRID 594185 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH2:10][C@@H:11]3[N:17]([CH:18]=2)[C:16](=[O:19])[C:15]2[CH:20]=[C:21]([O:62][CH3:63])[C:22]([O:24][CH2:25][CH2:26][CH2:27][O:28][C:29]4[C:59]([O:60][CH3:61])=[CH:58][C:32]5[C:33](=[O:57])[N:34]6[CH:49]=[C:48](S(C(F)(F)F)(=O)=O)[CH2:47][C@H:35]6[C:36](=[O:46])[N:37]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:45])([CH3:44])[CH3:43])[C:31]=5[CH:30]=4)=[CH:23][C:14]=2[N:13]([CH2:64][O:65][CH2:66][CH2:67][Si:68]([CH3:71])([CH3:70])[CH3:69])[C:12]3=[O:72])=[CH:5][CH:4]=1.[NH2:73][C:74]1[CH:79]=[CH:78][CH:77]=[CH:76][C:75]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C.CCCCCC>C(O)C.C1(C)C=CC=CC=1.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:73][C:74]1[CH:79]=[CH:78][CH:77]=[CH:76][C:75]=1[C:48]1[CH2:47][C@@H:35]2[N:34]([CH:49]=1)[C:33](=[O:57])[C:32]1[CH:58]=[C:59]([O:60][CH3:61])[C:29]([O:28][CH2:27][CH2:26][CH2:25][O:24][C:22]3[C:21]([O:62][CH3:63])=[CH:20][C:15]4[C:16](=[O:19])[N:17]5[CH:18]=[C:9]([C:6]6[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=6)[CH2:10][C@H:11]5[C:12](=[O:72])[N:13]([CH2:64][O:65][CH2:66][CH2:67][Si:68]([CH3:69])([CH3:71])[CH3:70])[C:14]=4[CH:23]=3)=[CH:30][C:31]=1[N:37]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:43])([CH3:44])[CH3:45])[C:36]2=[O:46]

Participants

10

Reactant 4

HCID 10340Sodium CarbonateHCID 2773216(2-Aminophenyl)boronic acidHCID 21226206Ethyl acetate hexaneHCID 86676188HCID 86676188, compound

Product 1

HCID 86676192(S)-2-(2-aminophenyl)-7-methoxy-8-(3-(((S)-7-methoxy-2-(4-methoxyphenyl)-5,11-dioxo-10((2-(trimethylsilyl)ethoxy)methyl)-5,10,11,11a-tetrahydro-pyrrolo[2,1-c][1,4]benzodiazepin-8-yl)oxy)propoxy)-10-((2-(trimethylsilyl)ethoxy)methyl)-pyrrolo[2,1-c][1,4]-benzodiazepine-5,11(10H,11aH)-dioneYield 90.3%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A catalytic amount of tetrakistriphenylphosphinepalladium (0) (11.2 mg) was added to a mixture of the mono triflate 17 (380 mg), the pinnacol ester of 2-aminophenylboronic acid (124 mg) and sodium carbonate (120 mg) in ethanol (5 mL), toluene (5 mL) and water (5 mL). The reaction mixture was allowed to stir over night at room temperature and at 40° C. until the reaction was complete (c. 2 hr). The reaction mixture was diluted with ethyl acetate and the organic layer was washed with water and brine. The ethyl acetate solution was dried over magnesium sulphate and filtered under vacuum. Removal of ethyl acetate by rotary evaporation under reduced pressure afforded the crude product which was subjected to flash chromatography (silica gel, ethyl acetate/hexane). Pure fractions were collected and combined. Removal of excess eluent by rotary evaporation under reduced pressure afforded the pure product 103 (330 mg, 86% yield). LC/MS RT: 4.17 min, ES+1018.48.

Workup

  1. custom(c. 2 hr)
  2. washthe organic layer was washed with water and brine
  3. dry with materialThe ethyl acetate solution was dried over magnesium sulphate
  4. filtrationfiltered under vacuum
  5. customRemoval of ethyl acetate
  6. customby rotary evaporation under reduced pressure
  7. customafforded the crude product which
  8. customPure fractions were collected
  9. customRemoval of excess eluent
  10. customby rotary evaporation under reduced pressure

Sources & evidence

ORD record
ord-a92c967aabcf4731b4bdbaf5618861cb
Source dataset
uspto-grants-2016_01
Patent number
US09242013B2

Reaction notes

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