Ethyl Acetate → HCID 118081947, compound

HRID 928156Notes

Reaction equation

HRID 928156 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)=[CH:17][CH:16]=2)[N:3]=1.[C:28]([O:32][C:33](=[O:40])[NH:34][C@H:35]1[CH2:39][CH2:38][NH:37][CH2:36]1)([CH3:31])([CH3:30])[CH3:29].C([O-])([O-])=O.[Cs+].[Cs+].C(OCC)(=O)C>C(O)(CC)(C)C.Cl[Pd-](P(C1CC2CC1CC2)C1CC2CC1CC2)[C-]1C=CC=C1CN(C)C.[CH-]1C=CC=C1.[Fe+2]>[NH3:3].[CH:11]([N:8]1[CH:7]=[N:6][C:5]2[C:9]1=[N:10][C:2]([N:37]1[CH2:38][CH2:39][C@H:35]([NH:34][C:33](=[O:40])[O:32][C:28]([CH3:30])([CH3:29])[CH3:31])[CH2:36]1)=[N:3][C:4]=2[NH:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]2[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]2)=[CH:17][CH:16]=1)([CH3:13])[CH3:12]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 118073643HCID 118073643, compound

Product 2

HCID 222AmmoniaHCID 118081947HCID 118081947, compoundYield 199.1%

Reagents, catalysts & solvents 2

HCID 178483166HCID 178483166, compoundCatalystHCID 64052-Methyl-2-butanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-chloro-9-isopropyl-N-(4-(4-methylpiperazin-1-yl)phenyl)-9H-purin -6-amine (2.32 g, 6 mmol), (S)-pyrrolidin-3-yl-carbamic acid tert-butyl ester (1.45 g, 7.8 mmol, 1.3 mol eq), and Cs2CO3 (7.82 g, 24 mmol, 4 mol eq) in tert-pentyl alcohol (60 mL, 0.1 M) was degassed with nitrogen. Chloro(di-2-norbornylphosphino)(2-dimethylaminomethylferrocen-1-yl)palladium(II) (CAS #614753-51-4, 375 mg, 0.6 mmol, 0.1 mol eq) was added, and the mixture degassed for 1 additional min. The vial was capped, stirred and heated at 100° C. (block temperature) for 20 hr. The reaction was cooled, diluted with water (25 mL) and ethyl acetate (150 mL) and the organic layer was separated. The aqueous layer was extracted with more ethyl acetate (50 mL) and the combined organics were dried over Na2SO4 and evaporated to give a residue that was purified via silica flash chromatography with a gradient of 50% heptane-50% ethyl acetate to 100% ethyl acetate and then to 10% ammonia (7 N in methanol)-90% ethyl acetate to give the title product as a light yellow solid (3.20 g, 99% yield). 1H NMR (400 MHz, DMSO d6) δ ppm 9.14 (s, 1 H) 7.90 (s, 1 H) 7.85 (d, J=9.05 Hz, 2 H) 7.14 (d, J=5.01 Hz, 1 H) 6.87 (d, J=9.17 Hz, 2 H) 4.61 (quin, J=6.72 Hz, 1 H) 4.05-4.27 (m, 2 H) 3.60-3.80 (m, 2 H) 3.50 (dt, J=10.55, 7.08 Hz, 1 H) 3.35 (dd, J=10.82, 4.83 Hz, 1 H) 3.02-3.11 (m, 4 H) 2.40-2.48 (m, 4 H) 2.22 (s, 3 H) 1.79-1.92 (m, 1 H) 1.50 (d, J=6.85 Hz, 6 H) 1.40 (s, 9 H). m/z (APCI+) for C28H41N9O2 536.4 (M+H)+.

Workup

  1. customwas degassed with nitrogen
  2. customthe mixture degassed for 1 additional min
  3. customThe vial was capped
  4. temperatureThe reaction was cooled
  5. additiondiluted with water (25 mL) and ethyl acetate (150 mL)
  6. customthe organic layer was separated
  7. extractionThe aqueous layer was extracted with more ethyl acetate (50 mL)
  8. dry with materialthe combined organics were dried over Na2SO4
  9. customevaporated
  10. customto give a residue that
  11. customwas purified via silica flash chromatography with a gradient of 50% heptane-50% ethyl acetate to 100% ethyl acetate

Sources & evidence

ORD record
ord-97767bc14e374c69a8a64ea44dfe8e1c
Source dataset
uspto-grants-2016_03
Patent number
US09290496B2

Reaction notes

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