Phosphorus oxychloride → 5-(4-Bromobenzyl)-7,8-dihydro-[1,3]dioxolo[4,5-g]isoquinoline
Reaction equation
C(OC([N:8]1[CH2:17][CH2:16][C:15]2[CH:14]=[C:13]3[O:18][CH2:19][O:20][C:12]3=[CH:11][C:10]=2[CH:9]1[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][CH:23]=1)=O)(C)(C)C.Cl.O1C2C=CC(CCN)=CC=2OC1.BrC1C=CC(CC(O)=O)=CC=1.O=P(Cl)(Cl)Cl>CN(C=O)C.C(#N)C.C(N(CC)CC)C>[Br:28][C:25]1[CH:24]=[CH:23][C:22]([CH2:21][C:9]2[C:10]3[CH:11]=[C:12]4[O:20][CH2:19][O:18][C:13]4=[CH:14][C:15]=3[CH2:16][CH2:17][N:8]=2)=[CH:27][CH:26]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Procedure
The synthesis of N-(2-Benzo[1,3]dioxol-5-yl-ethyl)-2-(4-bromophenyl)acetamide 35, 5-(4-bromobenzyl)-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinoline oxalate salt 37, and 5-(4-Bromobenzyl)-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinoline-6-carboxylic acid tert-butyl ester 38 is shown in scheme-10. Compound 35 was synthesized by coupling of 2-Benzo[1,3]dioxol-5-yl-ethylamine hydrochloride salt 33 with 4-bromophenyl acetic acid 34 using diethyl cyanophosphonate in the presence of triethyl amine in DMF. The amide 35 was cyclized by Bischler Napieralski reaction using POCl3 in anhydrous acetonitrile to get 5-(4-bromobenzyl)-7,8-dihydro-[1,3]dioxolo[4,5-g]isoquinoline 36 which was reduced by NaBH4 and converted to an oxalate salt 37 using oxalic acid dihydrate in methanol. The compound 37 was treated with 1N NaOH in dichloromethane to obtain free amine and this amine was protected with di-tert-butyl dicarbonate in the presence of 1N NaOH in THF to afford compound 38.
Sources & evidence
- ORD record
- ord-cafa96923d6549f4be9628fee9d86d9f
- Source dataset
- uspto-grants-2013_08
- Patent number
- US08507523B2
Reaction notes
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