Lithium Hydroxide → 6-(7H-Pyrrolo[2,3-d]pyrimidin-5-yl)-3',6'-dihydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl ester

HRID 2039722Notes

Reaction equation

HRID 2039722 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]2[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:12][CH:13]=2)[CH:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:29]2[C:37]3[CH:36]=[N:35][CH:34]=[N:33][C:32]=3[N:31](S(C3C=CC(C)=CC=3)(=O)=O)[CH:30]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Li+]>COCCOC.CCOC(C)=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:17]([O:16][C:14]([N:11]1[CH2:12][CH:13]=[C:8]([C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([C:29]3[C:37]4[CH:36]=[N:35][CH:34]=[N:33][C:32]=4[NH:31][CH:30]=3)[N:7]=2)[CH2:9][CH2:10]1)=[O:15])([CH3:20])([CH3:19])[CH3:18]

Participants

8

Reactant 4

HCID 3939Lithium HydroxideHCID 10340Sodium CarbonateHCID 693263825-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-7-tosyl-7h-pyrrolo[2,3-d]pyrimidine2×HCID 86614830tert-Butyl 6-bromo-3',6'-dihydro-2,4'-bipyridine-1'(2'H)-carboxylate

Product 1

HCID 161177416-(7H-Pyrrolo[2,3-d]pyrimidin-5-yl)-3',6'-dihydro-2'H-[2,4']bipyridinyl-1'-carboxylic acid tert-butyl esterYield 43.2%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

As shown in FIG. 7—step iii, a mixture of compound 1032 (0.18 g), 5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-7-(toluene-4-sulfonyl)-7H-pyrrolo[2,3-d]pyrimidine (compound 1005, 0.20 g), tetrakis(triphenylphosphine) palladium (50 mg), and 2N sodium carbonate (0.8 mL) in DME (5 mL) was heated at 90° C. overnight. Saturated aqueous lithium hydroxide (2 mL) was added and the reaction was heated at 60° C. for 1 hour. The reaction mixture was diluted with EtOAc and washed with brine. The organics were dried over sodium sulfate, concentrated, and purified by chromatography (SiO2, 50% ethyl acetate/hexane) to afford 6-(7H-Pyrrolo[2,3-d]pyrimidin-5-yl)-3′,6′-dihydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester (compound 1033, 81.6 mg).

Workup

  1. temperaturethe reaction was heated at 60° C. for 1 hour
  2. washwashed with brine
  3. dry with materialThe organics were dried over sodium sulfate
  4. concentrationconcentrated
  5. custompurified by chromatography (SiO2, 50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-29b5b7c308bd4b94aea839e8302040ec
Source dataset
uspto-grants-2013_11
Patent number
US08580802B2

Reaction notes

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