Dichloromethane → HCID 178423523, compound

HRID 1640307Notes

Reaction equation

HRID 1640307 reaction equation
FC(F)(F)C(O)=O.[CH3:8][C:9]1[CH:14]=[C:13]([C:15]2[N:19](C3CCCCO3)[CH:18]=[N:17][N:16]=2)[CH:12]=[CH:11][C:10]=1[C:26]1[N:31]=[C:30]2[NH:32][C:33]3([CH2:38][CH2:37]3)[C:34](=[O:36])[NH:35][C:29]2=[N:28][CH:27]=1.CC1C=C(C2N(C3CCCCO3)C=NN=2)C=CC=1B1OC(C)(C)C(C)(C)O1.BrC1N=C2NC3(CC3)C(=O)NC2=NC=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>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].C(O)(C)C.O1CCOCC1>[CH3:8][C:9]1[CH:14]=[C:13]([C:15]2[NH:19][CH:18]=[N:17][N:16]=2)[CH:12]=[CH:11][C:10]=1[C:26]1[N:31]=[C:30]2[NH:32][C:33]3([CH2:37][CH2:38]3)[C:34](=[O:36])[NH:35][C:29]2=[N:28][CH:27]=1

Participants

9

Reactant 5

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 533752283-(3-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazoleHCID 666081077'-(2-Methyl-4-(4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-1'H-spiro[cyclopropane-1,2'-pyrazino[2,3-b]pyrazin]-3'(4'H)-one trifluoroacetateHCID 866446477'-bromo-1'H-spiro[cyclopropane-1,2'-pyrazino[2,3-b]pyrazin]-3'(4'H)-one

Product 1

HCID 178423523HCID 178423523, compoundYield 38%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 3776IsopropanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

7′-(2-Methyl-4-(4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-1′H-spiro[cyclopropane-1,2′-pyrazino[2,3-b]pyrazin]-3′(4′H)-one trifluoroacetate. 3-(3-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazole (See Example 2.C) (0.201 g, 0.545 mmol), 7′-bromo-1′H-spiro[cyclopropane-1,2′-pyrazino[2,3-b]pyrazin]-3′(4′H)-one (0.139 g, 0.545 mmol), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.045 g, 0.054 mmol), sodium carbonate (1 M in water, 1.635 mL, 1.635 mmol), 1,4-dioxane (1.2 mL) and isopropanol (0.4 mL) were combined in a sealable vessel with a stirbar. The system was purged with nitrogen. The resulting mixture was sealed, stirred vigorously and heated at 100° C. for 1 h. The resulting mixture was diluted with water and extracted three times with dichloromethane. The combined organics were concentrated under reduced pressure. The residue was taken up in DMSO and methanol, filtered and purified using reverse-phase preparatory HPLC (20-70% acetonitrile+0.1% TFA in water+0.1% TFA, over 30 min). Fractions containing the desired product were combined and the solvent removed under reduced pressure. The residue was dried under high vacuum to give the desired product (0.109 g, 0.205 mmol, 38% yield) as an orange solid. MS (ESI) m/z 418.4 [M+1]+.

Workup

  1. customThe system was purged with nitrogen
  2. customThe resulting mixture was sealed
  3. additionThe resulting mixture was diluted with water
  4. extractionextracted three times with dichloromethane
  5. concentrationThe combined organics were concentrated under reduced pressure
  6. filtrationmethanol, filtered
  7. custompurified
  8. customreverse-phase preparatory HPLC (20-70% acetonitrile+0.1% TFA in water+0.1% TFA, over 30 min)
  9. additionFractions containing the desired product
  10. customthe solvent removed under reduced pressure
  11. customThe residue was dried under high vacuum

Sources & evidence

ORD record
ord-b0be13d7519e475193524613fdde7568
Source dataset
uspto-grants-2012_02
Patent number
US08110578B2

Reaction notes

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