Cyclopropanemethanamine → 4-Chloro-2-(4-cyclopropylmethyl-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid

HRID 1927504Notes

Reaction equation

HRID 1927504 reaction equation
[CH:1]1([CH2:4][NH2:5])[CH2:3][CH2:2]1.Cl[CH2:7][CH2:8][N:9]([CH2:32][CH2:33]Cl)[C:10]1[CH:30]=[C:29]([Cl:31])[C:13]2[O:14][C:15]3[C:24]([CH3:25])=[CH:23][C:22]([C:26]([OH:28])=[O:27])=[CH:21][C:16]=3[S:17](=[O:20])(=[O:19])[CH2:18][C:12]=2[CH:11]=1>CO>[Cl:31][C:29]1[C:13]2[O:14][C:15]3[C:24]([CH3:25])=[CH:23][C:22]([C:26]([OH:28])=[O:27])=[CH:21][C:16]=3[S:17](=[O:20])(=[O:19])[CH2:18][C:12]=2[CH:11]=[C:10]([N:9]2[CH2:8][CH2:7][N:5]([CH2:4][CH:1]3[CH2:3][CH2:2]3)[CH2:33][CH2:32]2)[CH:30]=1

Participants

4

Reactant 2

HCID 75646CyclopropanemethanamineHCID 1317284742-[Bis-(2-chloroethyl)amino]-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]-cycloheptene-8-carboxylic acid

Product 1

HCID 1317284864-Chloro-2-(4-cyclopropylmethyl-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Cyclopropylmethyl amine (0.30 mL, 3.34 mmol) was added to a solution of Example 102j (0.2 g, 0.42 mmol) in methanol (5 mL), followed by the addition of n-tetrabutylammonium iodide (0.01 g, 0.020 mmol) in an atmosphere of nitrogen and sealed in a pressure reactor vessel at 110° C. for 10 h. The reaction mixture was brought to room temperature, concentrated, treated with water and extracted with n-butanol. The organic layer was washed with water, brine, dried, concentrated and purified by crystallisation (ethylacetate-pet-ether). Yield: 0.114 g, (53.7%). 1H NMR (DMSO-d6): δ 0.1 (d, 2H, CH2), 0.50 (d, 2H, CH2), 0.90 (m, 1H, CH), 2.30 (d, 2H, CH2), 2.70 (s, 3H, CH3), 3.20-3.25 (m, 4H, 2CH2), 5.15 (s, 2H, CH2), 7.10 (s, 1H, Ar), 7.15 (s, 1H, Ar), 8.0 (s, 1H, Ar), 8.20 (s, 1H, Ar).

Workup

  1. customsealed in a pressure reactor vessel at 110° C. for 10 h
  2. customwas brought to room temperature
  3. concentrationconcentrated
  4. additiontreated with water
  5. extractionextracted with n-butanol
  6. washThe organic layer was washed with water, brine
  7. customdried
  8. concentrationconcentrated
  9. custompurified by crystallisation (ethylacetate-pet-ether)

Sources & evidence

ORD record
ord-75941bfe5f7143bfa1ffa8a4ab18bc1a
Source dataset
uspto-grants-2012_05
Patent number
US08183234B2

Reaction notes

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