Morpholine → HCID 178521260, compound

HRID 388149Notes

Reaction equation

HRID 388149 reaction equation
F[C:2](F)(F)[C:3](O)=O.Br[C:9]1[N:14]=[C:13]2[N:15]([CH2:19][C:20]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[O:21])[C:16](=[O:18])[NH:17][C:12]2=[N:11][CH:10]=1.BrC1[N:34]=[C:33]2[N:35](CC(O)=O)[C:36](=O)[NH:37]C2=NC=1.C(N1[CH:54]=[CH:53]N=C1)(N1C=CN=C1)=O.N1CCO[CH2:57][CH2:56]1>CN(C=O)C.C(Cl)Cl>[N:37]1[N:34]=[C:33]([C:3]2[CH:2]=[CH:54][C:53]([C:9]3[N:14]=[C:13]4[N:15]([CH2:19][C:20]([N:22]5[CH2:27][CH2:26][O:25][CH2:24][CH2:23]5)=[O:21])[C:16](=[O:18])[NH:17][C:12]4=[N:11][CH:10]=3)=[CH:57][CH:56]=2)[NH:35][CH:36]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 682631,1'-CarbonyldiimidazoleHCID 86626422HCID 86626422, compoundHCID 86658264HCID 86658264, compound

Product 1

HCID 178521260HCID 178521260, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

6-Bromo-1-(2-morpholino-2-oxoethyl)-1H-imidazo[4,5-b]pyrazin-2(3H)-one 2,2,2-trifluoroacetate. 2-(6-Bromo-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-1-yl)acetic acid (141 mg, 0.516 mmol) and 1,1′-carbonyldiimidazole (256 mg, 1.58 mmol) were combined in a round-bottom flask with a stirbar. Methylene chloride (6 mL) was added and the resulting mixture stirred at room temperature under nitrogen. DMF (2 mL) was added. All of the solids dissolved. The resulting clear reaction mixture was stirred at room temperature under nitrogen for 2.5 h at which time morpholine (0.34 mL, 3.90 mmol) was added. The resulting mixture was stirred at room temperature for 1 h. The methylene chloride was removed on a rotary evaporator. The resulting mixture was diluted with methanol, filtered, and purified using reverse-phase preparatory HPLC (5-50% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). Vials containing product were combined and all of the solvent removed on a rotary evaporator. The residue was dried under vacuum to give the desired product (209 mg, 89%) as a slightly yellow foam-solid. 1 H NMR (400 MHz, DMSO-d6) δ 12.36 (s, 1H), 8.09 (s, 1H), 4.78 (s, 2H), 3.63-3.69 (m, 2H), 3.55-3.62 (m, 4H), 3.43 (t, J=4.88, 2H); MS (ESI) m/z 342 [M+1]+.

Workup

  1. dissolutionAll of the solids dissolved
  2. additionwas added
  3. stirringThe resulting mixture was stirred at room temperature for 1 h
  4. customThe methylene chloride was removed on a rotary evaporator
  5. additionThe resulting mixture was diluted with methanol
  6. filtrationfiltered
  7. custompurified
  8. customreverse-phase preparatory HPLC (5-50% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min)
  9. additionVials containing product
  10. customall of the solvent removed on a rotary evaporator
  11. customThe residue was dried under vacuum

Sources & evidence

ORD record
ord-506e0ee8078949ed97223dcdc0e05d7c
Source dataset
uspto-grants-2013_02
Patent number
US08372976B2

Reaction notes

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