Sodium Carbonate → (4-{4-[5-(6-Trifluoromethyl-pyridin-3-ylamino)-pyrazin-2-yl]-phenyl}-cyclohexyl)-acetic acid methyl ester

HRID 76083Notes

Reaction equation

HRID 76083 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9]2[CH:10]=[N:11][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:13][CH:14]=2)=[N:6][CH:7]=1.[CH3:19][O:20][C:21](=[O:42])[CH2:22][CH:23]1[CH2:28][CH2:27][CH:26]([C:29]2[CH:34]=[CH:33][C:32](C3C=CC(Br)=CN=3)=[CH:31][CH:30]=2)[CH2:25][CH2:24]1.C(=O)([O-])[O-].[Na+].[Na+]>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.COCCOC>[CH3:19][O:20][C:21](=[O:42])[CH2:22][CH:23]1[CH2:24][CH2:25][CH:26]([C:29]2[CH:30]=[CH:31][C:32]([C:2]3[CH:7]=[N:6][C:5]([NH:8][C:9]4[CH:10]=[N:11][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:13][CH:14]=4)=[CH:4][N:3]=3)=[CH:33][CH:34]=2)[CH2:27][CH2:28]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 66615782Methyl 2-[4-[4-(5-bromopyridin-2-yl)phenyl]cyclohexyl]acetateHCID 86634697(5-Bromopyrazin-2-yl)-(6-trifluoromethyl-pyridin-3-yl)-amine

Product 1

HCID 66615921(4-{4-[5-(6-Trifluoromethyl-pyridin-3-ylamino)-pyrazin-2-yl]-phenyl}-cyclohexyl)-acetic acid methyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
130 °C

Procedure

A solution of (5-Bromopyrazin-2-yl)-(6-trifluoromethyl-pyridin-3-yl)-amine (0.072 g) and {4-[4-(5-bromo-pyridin-2-yl)-phenyl]-cyclohexyl}-acetic acid methyl ester (0.087 g) in 2 Ml DME was charged with 2 M sodium carbonate (1 Ml) and Pd(PPh3)4 (0.027 g, 0.1 equiv). The biphasic mixture was sparged with nitrogen for 3 min, then stirred at 130° C. under microwave heating for 30 min. The reaction was partitioned between EtOAc and water, and the organic extracts were dried over magnesium sulphate and concentrated in vacuo. Purification by silica gel chromatography (33% EtOAc in hexanes) afforded the title compound: (M+H)+471.2.

Workup

  1. customThe biphasic mixture was sparged with nitrogen for 3 min
  2. temperatureheating for 30 min
  3. customThe reaction was partitioned between EtOAc and water
  4. dry with materialthe organic extracts were dried over magnesium sulphate
  5. concentrationconcentrated in vacuo
  6. customPurification by silica gel chromatography (33% EtOAc in hexanes)

Sources & evidence

ORD record
ord-9737d4bd15de43ed8bf00e5194056ba7
Source dataset
uspto-grants-2014_09
Patent number
US08835451B2

Reaction notes

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