Sodium Carbonate → Ethyl 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate

HRID 1630317Notes

Reaction equation

HRID 1630317 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].[Cl:28][C:29]1[C:38]2[NH:37][CH2:36][CH2:35][O:34][C:33]=2[CH:32]=[CH:31][C:30]=1B1OC(C)(C)C(C)(C)O1.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[C:30]1[CH:31]=[CH:32][C:33]2[O:34][CH2:35][CH2:36][NH:37][C:38]=2[C:29]=1[Cl:28])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 595786245-chloro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazineHCID 86691589HCID 86691589, compound

Product 1

HCID 71258189Ethyl 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °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 (400 mg, 0.817 mmol), 5-chloro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine (prepared according to the procedure described in WO 2009/062285; 290 mg, 0.981 mmol) and 2N Na2CO3 (0.817 mL, 1.635 mmol) in DMF (8 mL) was degassed for 15 min. Tetrakis(triphenylphosphine)palladium(0) (66.1 mg, 0.057 mmol) was added and the degassing was continued for another 5 min. The mixture was then heated at 90° C. for 16 h. At this point LCMS indicated completion of reaction and presence of desired product. After cooling to room temperature, water was added (25 mL) and the mixture was extracted with ethyl acetate (2×100 mL), washed with brine (100 mL), dried (Na2SO4), filtered and concentrated. The crude was purified by biotage (5-70% EtOAc/hexane) to afford ethyl 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(5-chloro-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (315 mg, 0.593 mmol, 72.6% yield) as a mixture of two atrope isomers which are not separable (approx 10-15% of minor atrope isomer present by LCMS and NMR). Mixture was used as is in the next step without further purification.

Workup

  1. customprepared

Sources & evidence

ORD record
ord-023333367f964c098cd56fc6ea271a19
Source dataset
uspto-grants-2014_07
Patent number
US08791108B2

Reaction notes

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