Dimethylamine → HCID 57904918, compound

HRID 1093144Notes

Reaction equation

HRID 1093144 reaction equation
[F:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]3[C:18]4([NH:21][CH2:22][CH2:23][OH:24])[CH2:19][CH2:20][CH:15]([CH2:16][CH2:17]4)[CH2:14][N:13]3[C:25](=[O:28])[C:26]=2[OH:27])=[O:9])=[CH:4][CH:3]=1.C([N:34]([CH:37](C)C)[CH2:35]C)(C)C.Cl[C:41](=O)[C:42](OC)=[O:43].CNC.C([OH:52])C>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]3[C:18]4([N:21]([CH2:41][CH2:42][OH:43])[C:22](=[O:52])[C:23]([N:34]([CH3:35])[CH3:37])=[O:24])[CH2:17][CH2:16][CH:15]([CH2:20][CH2:19]4)[CH2:14][N:13]3[C:25](=[O:28])[C:26]=2[OH:27])=[O:9])=[CH:29][CH:30]=1

Participants

7

Reactant 5

HCID 674DimethylamineHCID 702EthanolHCID 79846Methyl chloroglyoxylateHCID 81531DiisopropylethylamineHCID 57904968HCID 57904968, compound

Product 1

HCID 57904918HCID 57904918, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of N-(4-fluorobenzyl)-3-hydroxy-10-((2-hydroxyethyl)amino)-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxamide (0.3358 g, 0.633 mmol) in CH2Cl2 (10 mL) with diisopropyl ethylamine (0.553 mL, 3.17 mmol) was cooled to 0° C. Methyl 2-chloro-2-oxoacetate (0.233 mL, 2.53 mmol) was added and the yellow solution stirred for 5 h, gradually warming to room temperature. The reaction was quenched with water and the organic phase was washed with 1N HCl, dried (Na2SO4), filtered and concentrated to give a yellow foam which was dissolved in hot ethanol (10 mL) and treated with 2M dimethylamine (1.583 mL, 3.17 mmol). The resulting yellow solution was stirred in a sealed tube at 85° C. for 18 h. The solution was concentrated and purified by preparative HPLC to give the title compound as a white solid (0.1692 g, 52% yield). 1H NMR (500 MHz, CDCl3) δ: 12.20 (1 H, brs), 9.71 (1 H, brs), 7.34 (2 H, dd, J=8.55, 5.49 Hz), 6.98 (2 H, t, J=8.70 Hz), 4.69 (1 H, dd, J=15.56, 7.63 Hz), 4.50-4.57 (1 H, m), 4.37-4.48 (2 H, m), 3.84-3.91 (1 H, m), 3.75-3.81 (1 H, m), 3.56-3.70 (3 H, m), 3.41-3.51 (1 H, m), 2.97 (3 H, s), 2.96 (3 H, s), 2.49 (1 H, brs), 1.98-2.14 (3 H, m), 1.71-1.91 (3 H, m), 1.38-1.47 (1 H, m). LCMS (M+H)=516.07. HPLC purity: >95%.

Workup

  1. customThe reaction was quenched with water
  2. washthe organic phase was washed with 1N HCl
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a yellow foam which
  7. stirringThe resulting yellow solution was stirred in a sealed tube at 85° C. for 18 h
  8. concentrationThe solution was concentrated
  9. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-807d93d41cb04b669c40060665d98583
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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