1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 178452920, compound

HRID 1639645Notes

Reaction equation

HRID 1639645 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[C:10]([C:14]([OH:16])=O)=[N:11][NH:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:17]1([C:23]2[C:24]([CH3:31])=[C:25]([NH2:30])[C:26]([NH2:29])=[CH:27][CH:28]=2)[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]1[C:10]([C:14](=[O:16])[NH:30][C:25]2[CH:24]=[CH:31][C:28]([CH2:23][N:17]3[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)=[CH:27][C:26]=2[NH2:29])=[N:11][NH:12][CH:13]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 667217534-Morpholin-4-yl methyl-benzene-1,2-diamineHCID 178452921HCID 178452921, compound

Product 1

HCID 178452920HCID 178452920, compoundYield 88.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-tert-Butoxycarbonylamino-1H-pyrazole-3-carboxylic acid (0.750 Kg, 3.30 mol, 1.0 wt), 4-morpholin-4-yl-methyl-benzene-1,2-diamine (0.752 Kg, 3.63 mol, 1.0 wt) and N,N′-dimethylformamide (11.25 L, 15.0 vol) were charged under nitrogen to a flange flask equipped with a mechanical stirrer and thermometer. 1-Hydroxybenzotriazole (HOBT, 0.540 Kg, 3.96 mol, 0.72 wt) was added at 15 to 25° C. N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide (EDC, 0.759 Kg, 3.96 mol, 1.01 wt) was added at 15 to 25° C. and the mixture was stirred at this temperature for 16 to 24 hours. Reaction completion was determined by 1H NMR analysis. The reaction mixture was concentrated under vacuum at 35 to 45° C. The residue was partitioned between ethyl acetate (7.50 L, 10.0 vol) and sat. aq. sodium hydrogen carbonate solution (8.03 L, 10.7 vol) and the layers were separated. The organic phase was washed with brine (3.75 L, 5.0 vol), dried over magnesium sulfate (1.00 Kg, 1.33 wt) and filtered. The filter-cake was washed with ethyl acetate (1.50 L, 2.0 vol). The combined filtrate and wash were concentrated under vacuum at 35 to 45° C. to give [3-(2-amino-4-morpholin-4-ylmethyl-phenylcarbamoyl)-1H-pyrazol-4-yl]-carbamic acid tert-butyl ester (1.217 Kg, 88.6%) as a dark brown solid.

Workup

  1. customequipped with a mechanical stirrer
  2. customReaction completion
  3. concentrationThe reaction mixture was concentrated under vacuum at 35 to 45° C
  4. customThe residue was partitioned between ethyl acetate (7.50 L, 10.0 vol) and sat. aq. sodium hydrogen carbonate solution (8.03 L, 10.7 vol)
  5. customthe layers were separated
  6. washThe organic phase was washed with brine (3.75 L, 5.0 vol)
  7. dry with materialdried over magnesium sulfate (1.00 Kg, 1.33 wt)
  8. filtrationfiltered
  9. washThe filter-cake was washed with ethyl acetate (1.50 L, 2.0 vol)
  10. washThe combined filtrate and wash
  11. concentrationwere concentrated under vacuum at 35 to 45° C.

Sources & evidence

ORD record
ord-7d263c1b88194adab4400da3190795d9
Source dataset
uspto-grants-2012_02
Patent number
US08110573B2

Reaction notes

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