Sodium Carbonate → Trifluoroacetic acid

HRID 1049128Notes

Reaction equation

HRID 1049128 reaction equation
[C:1]([CH2:3][C:4]1([N:23]2[CH:27]=[C:26](B3OC(C)(C)C(C)(C)O3)[CH:25]=[N:24]2)[CH2:7][N:6]([C:8]2[N:9]=[CH:10][C:11]([C:14]([NH:16][C@@H:17]([CH3:22])[C:18]([F:21])([F:20])[F:19])=[O:15])=[N:12][CH:13]=2)[CH2:5]1)#[N:2].Br[C:38]1[C:39]([CH3:50])=[N:40][N:41](C(OC(C)(C)C)=O)[CH:42]=1.[C:51](=[O:54])([O-])[O-:52].[Na+].[Na+]>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>[F:19][C:18]([F:21])([F:20])[C:51]([OH:52])=[O:54].[C:1]([CH2:3][C:4]1([N:23]2[CH:27]=[C:26]([C:38]3[C:39]([CH3:50])=[N:40][NH:41][CH:42]=3)[CH:25]=[N:24]2)[CH2:7][N:6]([C:8]2[N:9]=[CH:10][C:11]([C:14]([NH:16][C@@H:17]([CH3:22])[C:18]([F:19])([F:20])[F:21])=[O:15])=[N:12][CH:13]=2)[CH2:5]1)#[N:2].[C:51]([OH:52])([C:18]([F:21])([F:20])[F:19])=[O:54]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 53216939tert-Butyl 4-bromo-3-methyl-1H-pyrazole-1-carboxylateHCID 1236980915-{3-(Cyanomethyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-[(1S)-2,2,2-trifluoro-1-methylethyl]pyrazine-2-carboxamide

Product 2

HCID 6422Trifluoroacetic acidHCID 178434536HCID 178434536, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-{3-(cyanomethyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-[(1S)-2,2,2-trifluoro-1-methylethyl]pyrazine-2-carboxamide (27.0 mg, 0.0533 mmol), tert-butyl 4-bromo-3-methyl-1H-pyrazole-1-carboxylate (15 mg, 0.059 mmol), tetrakis(triphenylphosphine)palladium(0) (3.1 mg, 0.0027 mmol) and sodium carbonate (17.0 mg, 0.160 mmol) in 1,4-dioxane (1.6 mL) and water (0.8 mL) under nitrogen was stirred at 100° C. overnight. The reaction mixture was filtered, and purified by RP-HPLC (pH=2 conditions) to afford the desired product as TFA salt. 1H NMR (300 MHz, CD3OD) δ 8.73 (d, J=1.4 Hz, 1H), 8.18 (d, J=0.6 Hz, 1H), 7.98 (d, J=1.4 Hz, 1H), 7.91-7.79 (m, 2H), 4.84 (m, 1H), 4.81 (d, J=10.2 Hz, 2H), 4.60 (d, J=10.2 Hz, 2H), 3.59 (s, 2H), 2.44 (s, 3H), 1.43 (d, J=7.1 Hz, 3H) ppm. LCMS cacld. for C20H21F3N9O (M+1)+: m/z=460.2. Found: 460.0.

Workup

  1. filtrationThe reaction mixture was filtered
  2. custompurified by RP-HPLC (pH=2 conditions)

Sources & evidence

ORD record
ord-1aaf08520d50474294af537d9fdc0f37
Source dataset
uspto-grants-2016_07
Patent number
US09382231B2

Reaction notes

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