4-Methylmorpholine → HCID 11573599, compound

HRID 33746Notes

Reaction equation

HRID 33746 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[N:13]=[C:14]([CH2:17]OC(=O)C(C)(C)C)[S:15][CH:16]=2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].Cl.Cl.C(N1CCNCC1)(C)C.O[N:37]1[C:41]2C=[CH:43][CH:44]=[CH:45][C:40]=2N=N1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[CH:1]([N:4]1[CH2:5][CH2:6][N:7]([C:10]([C:12]2[N:13]=[C:14]([CH2:17][N:37]3[CH2:43][CH2:44][CH2:45][CH2:40][CH2:41]3)[S:15][CH:16]=2)=[O:11])[CH2:8][CH2:9]1)([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 122683781-Isopropylpiperazine dihydrochlorideHCID 44516088HCID 44516088, compound

Product 1

HCID 11573599HCID 11573599, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2,2-Dimethyl-Propionic acid 4-(4-isopropyl-piperazine-1-carbonyl)-thiazol-2-ylmethyl ester. The crude product from Step A (6.42 g, 24.2 mmol), 1-isopropyl-piperazine dihydrochloride (5.36 g., 26.68 mmol) and 1-hydroxybenzotriazole (4.915 g., 36.38 mmol) were dissolved into a mixture of N-methylmorpholine (14.72 g., 101.20 mmol) and DCM (120 mL). The mixture was stirred for 30 min under nitrogen. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (6.97 g, 36.4 mmol) was added, and the reaction mixture was stirred for 18 h at rt. The reaction was quenched by the addition of 1 M NaOH (25 mL), and was stirred for 1 h. The mixture was diluted with water and extracted with DCM (3×60 mL). The combined organic extracts were washed with H2O, dried over Na2SO4, filtered, and concentrated to yield dark brown crude oil (6.2 g). The crude product was purified on silica gel column using 30-50% acetone-DCM to give the title compound as a brown oil (3.9 g, 46%). 1H NMR (500 MHz, CDCl3): 7.89 (s, 1H), 5.38 (s, 2H), 3.90-3.84 (m, 2H), 3.81-3.75 (m, 2H), 2.75-2.69 (m, 1H), 2.62-2.50 (m, 4H), 1.27-1.23 (s, 9H), 1.05 (d, J=6.3, 6H).

Workup

  1. stirringthe reaction mixture was stirred for 18 h at rt
  2. customThe reaction was quenched by the addition of 1 M NaOH (25 mL)
  3. stirringwas stirred for 1 h
  4. additionThe mixture was diluted with water
  5. extractionextracted with DCM (3×60 mL)
  6. washThe combined organic extracts were washed with H2O
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto yield dark brown crude oil (6.2 g)
  11. customThe crude product was purified on silica gel column

Sources & evidence

ORD record
ord-b731e31383564775b6226ac1f7507634
Source dataset
uspto-grants-2008_09
Patent number
US07429659B2

Reaction notes

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