Hydrochloric Acid → HCID 69819410, compound

HRID 1006354Notes

Reaction equation

HRID 1006354 reaction equation
[ClH:1].Cl.Cl.[CH:4]([C@H:17]1[N:22]2[CH2:23][CH2:24][NH:25][CH2:26][C@H:21]2[CH2:20][N:19]([CH2:27][C:28]2[CH:33]=[C:32]([N:34]3[C:38]([C:39]([F:42])([F:41])[F:40])=[N:37][N:36]=[N:35]3)[CH:31]=[CH:30][C:29]=2[O:43][CH3:44])[CH2:18]1)([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH:45]1([C:50](O)=[O:51])[CH2:49][CH2:48][CH2:47][CH2:46]1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.Cl>ClCCl.C(OCC)(=O)C.CCCCCC.C(N(CC)CC)C>[ClH:1].[ClH:1].[CH:4]([C@H:17]1[N:22]2[CH2:23][CH2:24][N:25]([C:50]([CH:45]3[CH2:49][CH2:48][CH2:47][CH2:46]3)=[O:51])[CH2:26][C@H:21]2[CH2:20][N:19]([CH2:27][C:28]2[CH:33]=[C:32]([N:34]3[C:38]([C:39]([F:42])([F:41])[F:40])=[N:37][N:36]=[N:35]3)[CH:31]=[CH:30][C:29]=2[O:43][CH3:44])[CH2:18]1)([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 18840Cyclopentanecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86589651HCID 86589651, compound

Product 1

HCID 69819410HCID 69819410, compound

Reagents, catalysts & solvents 4

HCID 6344DichloromethaneSolventHCID 8058HexaneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a mixture of (4R,9aS)-4-benzhydryl-2-[2-methoxy-5-[5-(trifluoromethyl)-1H-tetrazol-1-yl]benzyl]octahydro-2H-pyrazino[1,2-a]pyrazine trihydrochloride (80 mg), cyclopentanecarboxylic acid (16.9 μl), 1-hydroxybenzotriazole hydrate (23 mg), and triethylamine (79 μl) in dichloromethane (1 ml) was added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride at room temperature. After stirring at room temperature overnight, the mixture was quenched with aqueous saturated sodium hydrogen carbonate and extracted with dichloromethane. The extract was dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified with preparative TLC (methanol/chloroform=1/9) to give an oil. To a solution of the oil in ethyl acetate (1 ml) was added 4N hydrogen chloride in ethyl acetate (0.2 ml) and hexane (20 ml). After stirring for 30 minutes, the precipitate was collected by filtration and dried under reduced pressure at 50° C. for 5 hours to give (4R,9aR)-4-benzhydryl-8-cyclopentanecarbonyl-2-[2-methoxy-5-[5-(trifluoromethyl)-1H-tetrazol-1-yl]benzyl]octahydro-2H-pyrazino[1,2-a]pyrazine dihydrochloride (63.9 mg) as a powder.

Workup

  1. customthe mixture was quenched with aqueous saturated sodium hydrogen carbonate
  2. extractionextracted with dichloromethane
  3. dry with materialThe extract was dried over magnesium sulfate
  4. customevaporated under reduced pressure
  5. customThe residue was purified with preparative TLC (methanol/chloroform=1/9)
  6. customto give an oil
  7. stirringAfter stirring for 30 minutes
  8. filtrationthe precipitate was collected by filtration
  9. customdried under reduced pressure at 50° C. for 5 hours

Sources & evidence

ORD record
ord-1d64b67789274f888259d36a5fe72093
Source dataset
uspto-grants-2004_09
Patent number
US06787543B2

Reaction notes

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