Diisopropylethylamine → (2S)-tert-butyl 2-(1-(7-chloropyrido[3,4-b]pyrazin-5-ylamino)ethyl)morpholine-4-carboxylate

HRID 57587Notes

Reaction equation

HRID 57587 reaction equation
[C:1]([C@H:4]1[O:9][CH2:8][CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5]1)(=O)[CH3:2].C([O-])(=O)C.[NH4+].[C:22]([BH3-])#[N:23].[Na+].ClC1[C:32]2=[N:33][CH:34]=[CH:35][N:36]=[C:31]2[CH:30]=[C:29]([Cl:37])[N:28]=1.CCN(C(C)C)C(C)C>CO>[Cl:37][C:29]1[N:28]=[C:22]([NH:23][CH:1]([C@H:4]2[O:9][CH2:8][CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5]2)[CH3:2])[C:32]2=[N:33][CH:34]=[CH:35][N:36]=[C:31]2[CH:30]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 717428275,7-Dichloropyrido(3,4-b)pyrazineHCID 86717375(S)-tert-butyl 2-acetylmorpholine-4-carboxylate

Product 1

HCID 86717374(2S)-tert-butyl 2-(1-(7-chloropyrido[3,4-b]pyrazin-5-ylamino)ethyl)morpholine-4-carboxylateYield 11.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of (S)-tert-butyl 2-acetylmorpholine-4-carboxylate (2.29 g, 10.0 mmol), ammonium acetate (7.70 g, 100 mmol), sodium cyanoborohydride (0.94 g, 15.0 mmol), and 5 angstrom molecular sieves (10 g) in methanol (50 mL) was stirred at room temperature under nitrogen for 16 hours. The sieves were removed by filtration and the filtrate was concentrated. A solution of 1 N NaOH was added until the pH reached 12. The mixture was extracted with CH2Cl2 and the combined extracts were dried over MgSO4, filtered and concentrated. The resulting light yellow oil (2.17 g) was dissolved in THF (40 mL) and 5,7-dichloropyrido[3,4-b]pyrazine (2.00 g, 10.0 mmol) and DIPEA (1.94 g, 15.0 mmol) were added. The mixture was heated to reflux for 48 hours. The volatile components were evaporated and the residue was extracted with ethyl acetate. Ethyl acetate was washed with brine and dried. The solvent was removed in vacuo. The crude residue was purified by silica-gel chromatography eluting with Hexane-50% EtOAc/Hexane (gradient) then C18 column to afford the subtitled compound as brown oil 450 mg. MS (m/z): 394 (M+H)+

Workup

  1. customThe sieves were removed by filtration
  2. concentrationthe filtrate was concentrated
  3. additionA solution of 1 N NaOH was added until the pH
  4. extractionThe mixture was extracted with CH2Cl2
  5. dry with materialthe combined extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe resulting light yellow oil (2.17 g) was dissolved in THF (40 mL)
  9. temperatureThe mixture was heated
  10. temperatureto reflux for 48 hours
  11. customThe volatile components were evaporated
  12. extractionthe residue was extracted with ethyl acetate
  13. washEthyl acetate was washed with brine
  14. customdried
  15. customThe solvent was removed in vacuo
  16. customThe crude residue was purified by silica-gel chromatography
  17. washeluting with Hexane-50% EtOAc/Hexane (gradient)

Sources & evidence

ORD record
ord-596760c7b58349b683084ab775891290
Source dataset
uspto-grants-2016_09
Patent number
US09434726B2

Reaction notes

Loading…