Sulfamide → (3R,4R)-3-[1-(2-sulfamoylamino-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1531514Notes

Reaction equation

HRID 1531514 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])=[CH:16][CH:15]=2)[C@@H:10]([O:34][CH2:35][C:36]2[CH:45]=[C:44]3[C:39]([CH2:40][CH2:41][CH2:42][N:43]3[CH2:46][CH2:47][NH2:48])=[CH:38][CH:37]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[S:49](N)([NH2:52])(=[O:51])=[O:50]>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])=[CH:16][CH:15]=2)[C@@H:10]([O:34][CH2:35][C:36]2[CH:45]=[C:44]3[C:39]([CH2:40][CH2:41][CH2:42][N:43]3[CH2:46][CH2:47][NH:48][S:49](=[O:51])(=[O:50])[NH2:52])=[CH:38][CH:37]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

4

Reactant 2

HCID 82267SulfamideHCID 69486181(3R,4R)-3-[1-(2-amino-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 69489189(3R,4R)-3-[1-(2-sulfamoylamino-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl esterYield 63.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 0.100 g (0.152 mmol) (3R,4R)-3-[1-(2-amino-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester [example 15(b)] and 0.029 g (0.303 mmol, 2.0 equiv.) of sulfamide in 3 ml of tetrahydrofuran was refluxed for 72 h. The reaction mixture was poured into 50 ml of an ice/water mixture and extracted three times with 50 ml of ethyl acetate. The combined organic phases were washed twice with 25 ml of water, evaporated under reduced pressure and dried in a high vacuum. The thus obtained crude product was purified by chromatography on silica gel using a 100:10:1 v/v/v mixture of dichloromethane/methanol/28% ammonium hydroxide solution as eluent to yield 0.071 g (0.096 mmol, 63.2% of theory) of (3R,4R)-3-[1-(2-sulfamoylamino-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-4 -[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester as a yellow oil; MS: 739 (M+H)+.

Workup

  1. extractionextracted three times with 50 ml of ethyl acetate
  2. washThe combined organic phases were washed twice with 25 ml of water
  3. customevaporated under reduced pressure
  4. customdried in a high vacuum
  5. customThe thus obtained crude product
  6. customwas purified by chromatography on silica gel using
  7. additiona 100:10:1 v/v/v mixture of dichloromethane/methanol/28% ammonium hydroxide solution as eluent

Sources & evidence

ORD record
ord-0a42930cbddd4cf7b3f811f0004d082c
Source dataset
uspto-grants-2001_03
Patent number
US06197959B1

Reaction notes

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