Water → 2-(5-(5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamide

HRID 510197Notes

Reaction equation

HRID 510197 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10](B3OC(C)(C)C(C)(C)O3)=[CH:9][N:8]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:5]2=[N:6][CH:7]=1.Br[C:29]1[CH:30]=[C:31]([NH:35][C@H:36]([CH:45]([CH3:47])[CH3:46])[C:37]([NH:39][CH2:40][C:41]([F:44])([F:43])[F:42])=[O:38])[CH:32]=[N:33][CH:34]=1.C([O-])([O-])=O.[Na+].[Na+].O>COCCOC.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:1][C:2]1[CH:3]=[C:4]2[C:10]([C:29]3[CH:30]=[C:31]([NH:35][CH:36]([CH:45]([CH3:47])[CH3:46])[C:37]([NH:39][CH2:40][C:41]([F:44])([F:43])[F:42])=[O:38])[CH:32]=[N:33][CH:34]=3)=[CH:9][N:8]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:25])([CH3:26])[CH3:27])[C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 89495326(R)-2-(5-bromopyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamideHCID 1269704485-chloro-3-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 1238640952-(5-(5-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamideYield 73.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a nitrogen gas purged mixture of 5-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine (231 mg, 0.565 mmol), (R)-2-(5-bromopyridin-3-ylamino)-3-methyl-N-(2,2,2-trifluoroethyl)butanamide (200 mg, 0.565 mmol), and Na2CO3 (847 μl, 1.694 mmol) in DME (3765 μl) was added Tetrakis (131 mg, 0.113 mmol). The reaction mixture was heated at 100° C. in a sealed microwave vessel for 1 h. Water (10 mL) was added and the mixture was extracted with ethyl acetate (2×20 mL). The combined organic extracts were dried with sodium sulfate, and concentrated under reduced pressure. Purification of the residue on silica (0-5% methanol/ethyl acetate, 25 gm silica) to give 232 mg foam, (2-1a).

Workup

  1. customTo a nitrogen gas purged
  2. extractionthe mixture was extracted with ethyl acetate (2×20 mL)
  3. dry with materialThe combined organic extracts were dried with sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customPurification of the residue on silica (0-5% methanol/ethyl acetate, 25 gm silica)

Sources & evidence

ORD record
ord-af61bf0d420447c98a0dcc0db88f4955
Source dataset
uspto-grants-2015_08
Patent number
US09096598B2

Reaction notes

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