Dichloromethane → methyl [4-(2-{(2S,4R)-1-[(1-carbamimidoyl-4-piperidinyl)carbonyl]-4-[1-(methylsulfonyl)-4-piperidinyl]-2-pyrrolidinyl}-1H-imidazol-5-yl)phenyl]carbamate dihydrochloride

HRID 1053837Notes

Reaction equation

HRID 1053837 reaction equation
CC(OC(=O)[NH:7][C:8]([N:17]1[CH2:22][CH2:21][CH:20]([C:23]([N:25]2[CH2:29][C@@H:28]([CH:30]3[CH2:35][CH2:34][N:33]([S:36]([CH3:39])(=[O:38])=[O:37])[CH2:32][CH2:31]3)[CH2:27][C@H:26]2[C:40]2[NH:41][C:42]([C:45]3[CH:50]=[CH:49][C:48]([NH:51][C:52]([O:54][CH3:55])=[O:53])=[CH:47][CH:46]=3)=[CH:43][N:44]=2)=[O:24])[CH2:19][CH2:18]1)=[N:9]C(=O)OC(C)(C)C)(C)C.FC(F)(F)C(O)=O.[Cl:64]CCl>>[ClH:64].[ClH:64].[C:8]([N:17]1[CH2:18][CH2:19][CH:20]([C:23]([N:25]2[CH2:29][C@@H:28]([CH:30]3[CH2:31][CH2:32][N:33]([S:36]([CH3:39])(=[O:38])=[O:37])[CH2:34][CH2:35]3)[CH2:27][C@H:26]2[C:40]2[NH:41][C:42]([C:45]3[CH:50]=[CH:49][C:48]([NH:51][C:52](=[O:53])[O:54][CH3:55])=[CH:47][CH:46]=3)=[CH:43][N:44]=2)=[O:24])[CH2:21][CH2:22]1)(=[NH:7])[NH2:9]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acid2×HCID 131736309bis(2-methyl-2-propanyl){[4-({(2S,4R)-2-(5-{4-[(methoxycarbonyl)amino]phenyl}-1H-imidazol-2-yl)-4-[1-(methylsulfonyl)-4-piperidinyl]-1-pyrrolidinyl}carbonyl)-1-piperidinyl]methylylidene}biscarbamate

Product 1

HCID 131736310methyl [4-(2-{(2S,4R)-1-[(1-carbamimidoyl-4-piperidinyl)carbonyl]-4-[1-(methylsulfonyl)-4-piperidinyl]-2-pyrrolidinyl}-1H-imidazol-5-yl)phenyl]carbamate dihydrochlorideYield 96%

Procedure

To a solution of the compound prepared in Example 68 (0.067 g, 0.084 mmol) in dichloromethane (2 mL) at 0° C. was added trifluoroacetic acid (0.09 mL, 1.2 mmol). The reaction was warmed to room temperature and stirred for 4 h whereupon the solvent and excess trifluoroacetic acid was removed in vacuo. The resulting residue was dissolved in methanol (5 mL) and 6 M hydrochloric acid (0.70 mL) was added. The mixture was concentrated to dryness and the process repeated twice. The residue was triturated with methanol and methyl tert-butyl ether, the resulting solids dissolved in water and lyophilized to afford the title compound (0.050 g, 96%) as a yellow solid.

Workup

  1. customwas removed in vacuo
  2. dissolutionThe resulting residue was dissolved in methanol (5 mL)
  3. addition6 M hydrochloric acid (0.70 mL) was added
  4. concentrationThe mixture was concentrated to dryness
  5. customThe residue was triturated with methanol and methyl tert-butyl ether
  6. dissolutionthe resulting solids dissolved in water

Sources & evidence

ORD record
ord-339322d014284556815dd640ae865fe8
Source dataset
uspto-grants-2016_07
Patent number
US09394250B2

Reaction notes

Loading…