Sodium Carbonate → (S)-tert-butyl 2-(4-chlorophenyl)-3-(4-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate

HRID 79548Notes

Reaction equation

HRID 79548 reaction equation
Br[C:2]1[C:3]([N:11]2[CH2:16][CH2:15][N:14]([C:17](=[O:38])[C@@H:18]([C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=3)[CH2:19][N:20]([CH:28]([CH3:30])[CH3:29])[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:13][CH2:12]2)=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.C([O-])([O-])=O.[Na+].[Na+].[CH3:45][N:46]1[CH:50]=[C:49](B2OC(C)(C)C(C)(C)O2)[CH:48]=[N:47]1>O1CCOCC1.O.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>[Cl:37][C:34]1[CH:35]=[CH:36][C:31]([C@H:18]([C:17]([N:14]2[CH2:13][CH2:12][N:11]([C:3]3[C:2]([C:49]4[CH:48]=[N:47][N:46]([CH3:45])[CH:50]=4)=[CH:7][N:6]=[C:5]4[NH:8][CH:9]=[CH:10][C:4]=34)[CH2:16][CH2:15]2)=[O:38])[CH2:19][N:20]([CH:28]([CH3:29])[CH3:30])[C:21](=[O:27])[O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[CH:32][CH:33]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 68764847(5)-Tert-butyl 3-(4-(5-bromo-1h-pyrrolo [2,3-b]pyridin-4-yl)piperazin-1-yl)-2-(4-chlorophenyl)-3-oxopropyl(isopropyl)carbamate

Product 1

HCID 68763031(S)-tert-butyl 2-(4-chlorophenyl)-3-(4-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamateYield 9.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

(S)-tert-Butyl 3-(4-(5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-2-(4-chlorophenyl)-3-oxopropyl(isopropyl)carbamate (0.05 g, 0.083 mmol, see Example 4) was placed in dioxane (1 mL) and Na2CO3 (aq., 0.087 g, 0.82 mmol) in H2O (0.3 mL). 1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.034 g, 0.16 mmol) and PS-Pd(PPh3)4 (0.075 g, 0.1 g/mmol) were then added. The reaction was heated to 150° C. in a microwave for 1 hour. The reaction was then diluted with water and extracted with DCM. The organic fractions were dried, filtered, and concentrated. Purification of the crude residue (500:10 to 500:20 DCM:MeOH) gave (S)-tert-butyl 2-(4-chlorophenyl)-3-(4-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate (0.005 g, 9.9% yield).

Workup

  1. extractionextracted with DCM
  2. customThe organic fractions were dried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification of the crude residue (500:10 to 500:20 DCM:MeOH)

Sources & evidence

ORD record
ord-0d8b112fbc384b9a9e5ac156370f8394
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

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