Water → Di-tert-butyl 1-[1-[3-(trifluoromethyl)benzyl]-2-({[3-(trifluoromethyl)benzyl]oxy}carbonyl)-1H-pyrrolo[3,2-b]pyridin-5-yl]hydrazine-1,2-dicarboxylate

HRID 628392Notes

Reaction equation

HRID 628392 reaction equation
Cl[C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:22]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=3)=[O:23])[N:10]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=3)[C:5]2=[CH:4][CH:3]=1.[NH:36]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[NH:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39].C([O-])([O-])=O.[Cs+].[Cs+].O>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>[F:19][C:18]([F:21])([F:20])[C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=1)[CH2:11][N:10]1[C:5]2[C:6](=[N:7][C:2]([N:36]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[NH:37][C:38]([O:40][C:41]([CH3:42])([CH3:43])[CH3:44])=[O:39])=[CH:3][CH:4]=2)[CH:8]=[C:9]1[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=1)=[O:23]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 85431Di-tert-butyl bicarbamateHCID 1181595373-(Trifluoromethyl)benzyl 5-chloro-1-[3-(trifluoromethyl)benzyl]-1H-pyrrolo[3,2-b]pyridine-2-carboxylate

Product 1

HCID 118159895Di-tert-butyl 1-[1-[3-(trifluoromethyl)benzyl]-2-({[3-(trifluoromethyl)benzyl]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-(trifluoromethyl)benzyl 5-chloro-1-[3-(trifluoromethyl)benzyl]-1H-pyrrolo[3,2-b]pyridine-2-carboxylate (3.2 g, 6.2 mmol, prepared as in Step 1), di-tert-butyl hydrazine-1,2-dicarboxylate (1.6 g, 6.9 mmol, Aldrich), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine-(2′-aminobiphenyl-2-yl)(chloro)palladium (1:1) (0.58 g, 0.74 mmol, Aldrich) and Cs2CO3 (2.2 g, 6.9 mmol) in toluene (71 mL) was heated at 110° C. for 2 hours. Upon cooling, water was added, and the layers were separated. The aqueous layer was further extracted with three portions of EtOAc. The combined organic extracts were dried over sodium sulfate, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-50% EtOAc in hexanes was used to purify the product. Yield: (0.28 g, 6% over the two steps). LCMS (M+H)+: 709.1.

Workup

  1. temperatureUpon cooling
  2. customthe layers were separated
  3. extractionThe aqueous layer was further extracted with three portions of EtOAc
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washFlash chromatography, eluting with a gradient from 0-50% EtOAc in hexanes
  8. customto purify the product

Sources & evidence

ORD record
ord-0bf9602f17754e58ae5a5bf7a1c7defc
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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