Hydrochloric Acid → HCID 25206610, compound

HRID 387671Notes

Reaction equation

HRID 387671 reaction equation
[O:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[CH:7]=[C:8]([C:24](O)=[O:25])[C:9]2[CH2:10][CH2:11][N:12]([CH:17]([CH2:21][CH2:22][CH3:23])[CH2:18][CH2:19][CH3:20])[C:13](=[O:16])[C:14]=2[CH:15]=1.[ClH:27].[NH2:28][C@@H:29]([CH2:47][C:48]1[CH:53]=[C:52]([F:54])[CH:51]=[C:50]([F:55])[CH:49]=1)[C@H:30]([OH:46])[CH2:31][NH:32][C:33]1([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([F:45])([F:44])[F:43])[CH:37]=2)[CH2:35][CH2:34]1.ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.Cl>CN(C)C=O.C(OCC)C.O1CCOCC1.C(OCC)(=O)C.O.C(N(CC)CC)C>[ClH:27].[F:54][C:52]1[CH:53]=[C:48]([CH:49]=[C:50]([F:55])[CH:51]=1)[CH2:47][C@H:29]([NH:28][C:24]([C:8]1[C:9]2[CH2:10][CH2:11][N:12]([CH:17]([CH2:18][CH2:19][CH3:20])[CH2:21][CH2:22][CH3:23])[C:13](=[O:16])[C:14]=2[CH:15]=[C:6]([C:2]2[O:1][CH:5]=[CH:4][N:3]=2)[CH:7]=1)=[O:25])[C@H:30]([OH:46])[CH2:31][NH:32][C:33]1([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([F:45])([F:43])[F:44])[CH:37]=2)[CH2:35][CH2:34]1

Participants

12

Reactant 5

HCID 313Hydrochloric AcidHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 684696977-(2-Oxazolyl)-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acidHCID 86643873HCID 86643873, compound

Product 1

HCID 25206610HCID 25206610, compoundYield 72.3%

Reagents, catalysts & solvents 6

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Added to a solution of 150 mg of 7-(2-oxazolyl)-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid in 4 cm3 of anhydrous dimethylformamide and under an argon atmosphere are 0.19 cm3 of triethylamine and 201 mg of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)butan-2-ol hydrochloride then 69 mg of 1-hydroxy-7-azabenzotriazole and 97 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. The solution is kept stirring for 15 h at a temperature close to 20° C. 50 cm3 of water and 50 cm3 of ethyl acetate are added to the reaction medium. After decanting, the organic phase is washed with 50 cm3 of a saturated aqueous solution of ammonium chloride, two lots of 20 cm3 of water and 20 cm3 of a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure (5 kPa). The residual solution (around 3 cm3) is filtered through a pellet of 15 g of 40-63 μm silica. The silica pellet is washed with 40 cm3 of ethyl acetate. The filtrate is concentrated to dryness under reduced pressure (5 kPa). 255 mg is obtained of a white powder which is dissolved in 10 cm3 of ethyl ether. Added thereto, while stirring, is 0.2 cm3 of a 4N solution of hydrochloric acid in dioxane at a temperature of 20° C. The reaction mixture precipitates. The precipitate is filtered, washed with two lots of 5 cm3 of isopropyl ether and dried under vacuum at a temperature of 35° C. 236 mg of N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-7-(2-oxazolyl)-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide hydrochloride are obtained in the form of white crystals.

Workup

  1. customclose to 20° C
  2. customAfter decanting
  3. washthe organic phase is washed with 50 cm3 of a saturated aqueous solution of ammonium chloride, two lots of 20 cm3 of water and 20 cm3 of a saturated aqueous solution of sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure (5 kPa)
  7. filtrationThe residual solution (around 3 cm3) is filtered through a pellet of 15 g of 40-63 μm silica
  8. washThe silica pellet is washed with 40 cm3 of ethyl acetate
  9. concentrationThe filtrate is concentrated to dryness under reduced pressure (5 kPa)
  10. custom255 mg is obtained of a white powder which
  11. additionAdded
  12. stirringwhile stirring
  13. customat a temperature of 20° C
  14. customThe reaction mixture precipitates
  15. filtrationThe precipitate is filtered
  16. washwashed with two lots of 5 cm3 of isopropyl ether
  17. customdried under vacuum at a temperature of 35° C

Sources & evidence

ORD record
ord-30d4b5331b524a0f89e27d293688cc42
Source dataset
uspto-grants-2013_02
Patent number
US08372864B2

Reaction notes

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