Ethylmorpholine → (R)-N-[(RS)-1-amidino-3-piperidinylmethyl]-alpha(2-naphthylsulfonamido)indole-3-propionamide bisulfite

HRID 1734300Notes

Reaction equation

HRID 1734300 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[S:11]([NH:14][C@@H:15]([C:26](O)=[O:27])[CH2:16][C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[NH:19][CH:18]=1)(=[O:13])=[O:12].C(N1CCOCC1)C.[S:37]([OH:40])([OH:39])=[O:38].[NH2:41][CH2:42][CH:43]1[CH2:48][CH2:47][CH2:46][N:45]([C:49](=[NH:51])[NH2:50])[CH2:44]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[S:37](=[O:38])([OH:40])[OH:39].[C:49]([N:45]1[CH2:46][CH2:47][CH2:48][CH:43]([CH2:42][NH:41][C:26](=[O:27])[C@H:15]([NH:14][S:11]([C:2]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=2)(=[O:13])=[O:12])[CH2:16][C:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[NH:19][CH:18]=2)[CH2:44]1)(=[NH:50])[NH2:51]

Participants

6

Reactant 4

HCID 7525EthylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 1800786(R)-3-(1H-Indol-3-yl)-2-(naphthalene-2-sulfonylamino)-propionic acidHCID 19080933Rac-3aminomethyl-1-amidinopiperidine sulphite

Product 1

HCID 22848479(R)-N-[(RS)-1-amidino-3-piperidinylmethyl]-alpha(2-naphthylsulfonamido)indole-3-propionamide bisulfiteYield 44.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1.5 g of N-(2-naphthylsulfonyl)-D-tryptophan in 30 ml of DMF is treated with 1.5 ml of ethylmorpholine. After the addition of 0.7 g of rac-3-aminomethyl-1-amidinopiperidine sulphite (Example 1)and 1.7 g of benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate the reaction mixture is stirred for 15 hours. The solvent is evaporated and the residue is taken up in 50 ml of water and extracted with 100 ml of ethyl acetate. The ethyl acetate phase is washed with water, dried and evaporated. The crude material is purified on a RP-18 column with water/acetonitrile (0-30%). There is obtained 0.8 g of (R)-N-[(RS)-1-amidino-3-piperidinylmethyl]-α(2-naphthylsulfonamido)indole-3-propionamide bisulfite, FAB-MS: 533 (M+H)+.

Workup

  1. customThe solvent is evaporated
  2. extractionextracted with 100 ml of ethyl acetate
  3. washThe ethyl acetate phase is washed with water
  4. customdried
  5. customevaporated
  6. customThe crude material is purified on a RP-18 column with water/acetonitrile (0-30%)

Sources & evidence

ORD record
ord-dbc5b0fd57c24d178424412bc422846c
Source dataset
uspto-grants-1996_07
Patent number
US05532232

Reaction notes

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