Potassium Carbonate → HCID 66693011, compound

HRID 472836Notes

Reaction equation

HRID 472836 reaction equation
[C:1]([O:5][C@@H:6]([C:11]1[C:12]([CH3:28])=[N:13][C:14]2[N:15]([N:18]=[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=3)[CH:20]=2)[C:16]=1Cl)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].[F:29][C:30]1[CH:31]=[C:32](B2OC(C)(C)C(C)(C)O2)[C:33]([CH3:40])=[C:34]2[C:39]=1[O:38][CH2:37][CH2:36][CH2:35]2.C([O-])([O-])=O.[K+].[K+]>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.CN(C=O)C>[C:1]([O:5][C@@H:6]([C:11]1[C:12]([CH3:28])=[N:13][C:14]2[N:15]([N:18]=[C:19]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=3)[CH:20]=2)[C:16]=1[C:32]1[C:33]([CH3:40])=[C:34]2[C:39](=[C:30]([F:29])[CH:31]=1)[O:38][CH2:37][CH2:36][CH2:35]2)[C:7]([O:9][CH3:10])=[O:8])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 596067662-(8-Fluoro-5-methylchroman-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86670278HCID 86670278, compound

Product 1

HCID 66693011HCID 66693011, compoundYield 37.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
125 °C

Procedure

To a 2-5 ml microwave tube was added (S)-methyl 2-(tert-butoxy)-2-(7-chloro-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (420 mg, 0.995 mmol), tetrakis(triphenylphosphine)palladium(0) (115 mg, 0.099 mmol), 2-(8-fluoro-5-methylchroman-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (320 mg, 1.094 mmol), DMF (4 mL), followed by 2M K2CO3 solution (400 μl). The reaction mixture was heated in a microwave reactor at 125° C. for 45 min. The reaction mixture was filtered and the filtrate was purified by silica gel chromatography to afford (204 mg, 37.2%) of the title compound. Enantiomeric Excess was determined by Chiral SFC method: Chiralpak AD-H analytical column, 4.6×250 mm, 5 μm. Mobile Phase: 15% MeOH in CO2. Temp: 35° C. Flow rate: 2.0 mL/min. for 10 min. UV monitored @ 266 nm. Injection: 5 uL of ˜2.0 mg/mL solution in 50:50 MeOH:CHCl3. The enantiomeric Excess is 93.0%. 1H NMR (500 MHz, CHLOROFORM-d) δ 7.83-7.78 (m, 1H), 7.69 (dt, J=6.7, 1.8 Hz, 1H), 7.35-7.28 (m, 2H), 6.87 (d, J=10.7 Hz, 1H), 6.84 (s, 1H), 5.00 (s, 1H), 4.48-4.26 (m, 2H), 3.64 (s, 3H), 2.85-2.67 (m, 5H), 2.30-2.13 (m, 2H), 1.84 (s, 3H), 1.16 (s, 9H).

Workup

  1. filtrationThe reaction mixture was filtered
  2. customthe filtrate was purified by silica gel chromatography

Sources & evidence

ORD record
ord-cf26914dcabe49b39f3334da40ea2507
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

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