Cesium carbonate → (R)-ethyl 5-(2-(2-(2-(tert-butoxycarbonylamino)ethylamino)-5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate

HRID 1426921Notes

Reaction equation

HRID 1426921 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[C:54]1[C:59]([C@H:60]2[CH2:64][CH2:63][CH2:62][N:61]2[C:65]2[CH:70]=[CH:69][N:68]3[N:71]=[CH:72][C:73]([C:74]([O:76][CH2:77][CH3:78])=[O:75])=[C:67]3[N:66]=2)=[CH:58][C:57]([F:79])=[CH:56][N:55]=1.[NH2:80][CH2:81][CH2:82][NH:83][C:84](=[O:90])[O:85][C:86]([CH3:89])([CH3:88])[CH3:87]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:86]([O:85][C:84]([NH:83][CH2:82][CH2:81][NH:80][C:54]1[C:59]([C@H:60]2[CH2:64][CH2:63][CH2:62][N:61]2[C:65]2[CH:70]=[CH:69][N:68]3[N:71]=[CH:72][C:73]([C:74]([O:76][CH2:77][CH3:78])=[O:75])=[C:67]3[N:66]=2)=[CH:58][C:57]([F:79])=[CH:56][N:55]=1)=[O:90])([CH3:89])([CH3:88])[CH3:87]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 187201N-BOC-ethylenediamineHCID 634876Binap, (A+-)-HCID 86664585(R)-ethyl 5-(2-(2-chloro-5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate

Product 1

HCID 86691721(R)-ethyl 5-(2-(2-(2-(tert-butoxycarbonylamino)ethylamino)-5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylateYield 58%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A mixture of Pd2 dba3 (7.05 mg, 0.00770 mmol), Cs2CO3 (125 mg, 0.385 mmol), rac-Binap (19.2 mg, 0.0308 mmol), (R)-ethyl 5-(2-(2-chloro-5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (50 mg, 0.128 mmol), and tert-butyl 2-aminoethylcarbamate (24.7 mg, 0.154 mmol) in degassed toluene (1 mL) was first purged with nitrogen, then sealed and subjected to microwave irradiation (120° C.) for 16 hours. After cooled to ambient temperature, the reaction mixture was diluted with EtOAc (10 mL) and washed with water (2×5 mL). The organic was dried (Na2SO4) and concentrated. The crude material was purified by reverse phase column chromatography (Biotage SP4 system C18 12+M cartridge, 5 to 70% acetonitrile/water) to yield the desired product as white foamy solid (38 mg, 58% yield). MS (apci) m/z=514.1 (M+H).

Workup

  1. customwas first purged with nitrogen
  2. customsealed
  3. customsubjected to microwave irradiation (120° C.) for 16 hours
  4. additionthe reaction mixture was diluted with EtOAc (10 mL)
  5. washwashed with water (2×5 mL)
  6. dry with materialThe organic was dried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude material was purified by reverse phase column chromatography (Biotage SP4 system C18 12+M cartridge, 5 to 70% acetonitrile/water)

Sources & evidence

ORD record
ord-fc6d7b2e0137467b8a64d72492f5c7c9
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

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