Dichloromethane → (S)-4-(2-chloro-8-cyclopropyl-9-methyl-9H-purin-6-yl)-3-methylmorpholine

HRID 2063363Notes

Reaction equation

HRID 2063363 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7](I)[N:8]2[CH3:11])=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][C@@H:14]2[CH3:19])[N:3]=1.[CH:20]1(B(O)O)[CH2:22][CH2:21]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].ClCCl>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:20]3[CH2:22][CH2:21]3)[N:8]2[CH3:11])=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][C@@H:14]2[CH3:19])[N:3]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 58222526(S)-4-(2-chloro-8-iodo-9-methyl-9H-purin-6-yl)-3-methylmorpholine

Product 1

HCID 58222533(S)-4-(2-chloro-8-cyclopropyl-9-methyl-9H-purin-6-yl)-3-methylmorpholineYield 71%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a high-pressure vessel was placed (S)-4-(2-chloro-8-iodo-9-methyl-9H-purin-6-yl)-3-methylmorpholine (78.2 mg, 0.20 mmol), cyclopropylboronic acid (25.8 mg, 0.30 mmol, 1.5 eq.), potassium phosphate (127.4 mg, 0.60 mmol, 3.0 eq.), [1,1′-bis-(diphenylphosphino)ferrocene]dichloropalladium (II), complexed with dichloromethane (1:1) (4.9 mg, 0.006 mmol, 0.03 eq.), and 1,4-dioxane (1.0 mL). The reaction mixture was degassed for 15 minutes. The vessel tube was sealed tightly, and the reaction mixture was stirred at 100° C. After 18 h the reaction was cooled to RT and diluted with ethyl acetate. The organic layer was washed with water and brine, then dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 80% ethyl acetate in hexane) to give the desired compound as a foam (43.7 mg, 71%). TLC (40% ethyl acetate/hexane), Rf=0.41; LC-MS m/z (method B2)=308 [M+H]+, RT=1.94 min.

Workup

  1. customIn a high-pressure vessel was placed
  2. customThe reaction mixture was degassed for 15 minutes
  3. customThe vessel tube was sealed tightly
  4. temperatureAfter 18 h the reaction was cooled to RT
  5. additiondiluted with ethyl acetate
  6. washThe organic layer was washed with water and brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 80% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-40a6e5b717c74ce1ae2adaa02dcd1bfb
Source dataset
uspto-grants-2012_10
Patent number
US08288381B2

Reaction notes

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