Sodium Carbonate → (S,E)-Ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-5-methyl-7-(4-methylpent-1-en-1-yl)pyrazolo[1,5-a]pyrimidine-2-carboxylate

HRID 1630324Notes

Reaction equation

HRID 1630324 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:27])=[N:14][C:15]2[N:16]([N:19]=[C:20]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:21]=2)[C:17]=1I)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[CH3:28][CH:29]([CH3:36])[CH2:30]/[CH:31]=[CH:32]/B(O)O.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:27])=[N:14][C:15]2[N:16]([N:19]=[C:20]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:21]=2)[C:17]=1/[CH:32]=[CH:31]/[CH2:30][CH:29]([CH3:36])[CH3:28])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 60815074-Methyl-1-pentenylboronic acidHCID 86691589HCID 86691589, compound

Product 1

HCID 71267861(S,E)-Ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-5-methyl-7-(4-methylpent-1-en-1-yl)pyrazolo[1,5-a]pyrimidine-2-carboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (S)-ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (300 mg, 0.613 mmol), (E)-(4-methylpent-1-en-1-yl)boronic acid (94 mg, 0.736 mmol) and 2N Na2CO3 (0.613 mL, 1.226 mmol) in DMF (6 mL) was degassed for 15 min. Tetrakis(triphenylphosphine)palladium(0) (49.6 mg, 0.043 mmol) was then added and the degassing was continued for another 5 min. The mixture was then heated at 100° C. for 2 h. At this point LCMS indicated completion of reaction and presence of desired product. After cooling to room temperature, water was added (10 mL) and the mixture was extracted with ether (2×50 mL), washed with brine (25 mL), dried (Na2SO4), filtered and concentrated. the crude was then purified by biotage (5-30% EtOAc/hexane) to afford (S,E)-ethyl 6-(1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-5-methyl-7-(4-methylpent-1-en-1-yl)pyrazolo[1,5-a]pyrimidine-2-carboxylate (200 mg, 0.449 mmol, 73.2% yield) as off-white solid. 1H NMR (500 MHz, CDCl3) δ 7.09 (s, 1H), 7.07 (s, 0.6H), 7.04 (s, 1H), 5.57 (s, 1H), 4.49 (q, J=7.1 Hz, 2H), 4.33-4.20 (m, 2H), 2.70 (s, 3H), 2.40 (td, J=7.0, 1.3 Hz, 2H), 1.90 (dt, J=13.4, 6.7 Hz, 1H), 1.46 (t, J=7.1 Hz, 3H), 1.29 (t, J=7.1 Hz, 3H), 1.17 (s, 9H), 1.06 (dd, J=6.6, 2.7 Hz, 6H). LCMS (M+H)=446.4.

Workup

  1. customwas degassed for 15 min

Sources & evidence

ORD record
ord-532f720e245d469a8d4ffc39d5078ac7
Source dataset
uspto-grants-2014_07
Patent number
US08791108B2

Reaction notes

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