Cesium carbonate → Di-tert-butyl 1-[1-[3-({[tert-butyl(diphenyl)silyl]oxy}methyl)-5-chlorobenzyl]-2-({[3-({[tert-butyl(diphenyl)silyl]oxy}methyl)-5-chlorobenzyl]oxy}carbonyl)-1H-pyrrolo[3,2-b]pyridin-5-yl]hydrazine-1,2-dicarboxylate

HRID 628387Notes

Reaction equation

HRID 628387 reaction equation
[Si:1]([O:18][CH2:19][C:20]1[CH:21]=[C:22]([CH:64]=[C:65]([Cl:67])[CH:66]=1)[CH2:23][N:24]1[C:32]2[C:27](=[N:28][C:29](Cl)=[CH:30][CH:31]=2)[CH:26]=[C:25]1[C:34]([O:36][CH2:37][C:38]1[CH:43]=[C:42]([Cl:44])[CH:41]=[C:40]([CH2:45][O:46][Si:47]([C:60]([CH3:63])([CH3:62])[CH3:61])([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH:39]=1)=[O:35])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:68]([C:77]([O:79][C:80]([CH3:83])([CH3:82])[CH3:81])=[O:78])[NH:69][C:70]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])=[O:71].C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.NC1C=CC=CC=1C1C=CC=CC=1[Pd]Cl>[Si:1]([O:18][CH2:19][C:20]1[CH:21]=[C:22]([CH:64]=[C:65]([Cl:67])[CH:66]=1)[CH2:23][N:24]1[C:32]2[C:27](=[N:28][C:29]([N:68]([C:77]([O:79][C:80]([CH3:83])([CH3:82])[CH3:81])=[O:78])[NH:69][C:70]([O:72][C:73]([CH3:74])([CH3:75])[CH3:76])=[O:71])=[CH:30][CH:31]=2)[CH:26]=[C:25]1[C:34]([O:36][CH2:37][C:38]1[CH:43]=[C:42]([Cl:44])[CH:41]=[C:40]([CH2:45][O:46][Si:47]([C:60]([CH3:63])([CH3:61])[CH3:62])([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[CH:39]=1)=[O:35])([C:14]([CH3:15])([CH3:16])[CH3:17])([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 85431Di-tert-butyl bicarbamateHCID 1237485193-({[tert-butyl(diphenyl)silyl]oxy}methyl)-5-chlorobenzyl 1-[3-({[tert-butyl(diphenyl)silyl]oxy}methyl)-5-chlorobenzyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-carboxylate

Product 1

HCID 131735350Di-tert-butyl 1-[1-[3-({[tert-butyl(diphenyl)silyl]oxy}methyl)-5-chlorobenzyl]-2-({[3-({[tert-butyl(diphenyl)silyl]oxy}methyl)-5-chlorobenzyl]oxy}carbonyl)-1H-pyrrolo[3,2-b]pyridin-5-yl]hydrazine-1,2-dicarboxylate

Reagents, catalysts & solvents 2

HCID 178439015HCID 178439015, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A degassed mixture of 3-({[tert-butyl(diphenyl)silyl]oxy}methyl)-5-chlorobenzyl 1-[3-({[tert-butyl(diphenyl)silyl]oxy}methyl)-5-chlorobenzyl]-5-chloro-1H-pyrrolo[3,2-b]pyridine-2-carboxylate (3.11 g, 3.16 mmol, from Step 4), di-tert-butyl hydrazine-1,2-dicarboxylate (0.81 g, 3.5 mmol, Aldrich), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (0.29 g, 0.37 mmol, Aldrich) and Cs2CO3 (1.1 g, 3.5 mmol) in toluene (36 mL) was sealed and heated at 110° C. for 4 hours. The reaction mixture was partitioned between water and ethyl acetate and the aqueous was extracted three times. The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The product was purified by flash chromatography, eluting with a gradient from 0-25% EtOAc in hexanes. Yield: (1.19 g, 32%).

Workup

  1. customwas sealed
  2. customThe reaction mixture was partitioned between water and ethyl acetate
  3. extractionthe aqueous was extracted three times
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe product was purified by flash chromatography
  8. washeluting with a gradient from 0-25% EtOAc in hexanes

Sources & evidence

ORD record
ord-dbf80a939ded4e82a6b62d6171e94f94
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

Loading…