HOAt → HCID 131730209, compound

HRID 387667Notes

Reaction equation

HRID 387667 reaction equation
Cl.[NH2:2][C@@H](CC1C=C(F)C=C(F)C=1)[C@H](O)CNC1(C2C=CC=C(C(F)(F)F)C=2)CC1.[CH3:30][S:31]([NH:34][C:35]1[CH:36]=[C:37]([C:53]([OH:55])=O)[C:38]2[CH2:39][CH2:40][N:41]([CH:46]([CH2:50][CH2:51][CH3:52])[CH2:47][CH2:48][CH3:49])[C:42](=[O:45])[C:43]=2[CH:44]=1)(=[O:33])=[O:32].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.C(OCC)(=O)C.O.C(N(CC)CC)C>[CH3:30][S:31]([NH:34][C:35]1[CH:36]=[C:37]([C:53]([NH2:2])=[O:55])[C:38]2[CH2:39][CH2:40][N:41]([CH:46]([CH2:50][CH2:51][CH3:52])[CH2:47][CH2:48][CH3:49])[C:42](=[O:45])[C:43]=2[CH:44]=1)(=[O:32])=[O:33]

Participants

9

Reactant 4

HCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68471216HCID 68471216, compoundHCID 86643873HCID 86643873, compound

Product 1

HCID 131730209HCID 131730209, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

Added to a solution of 185 mg of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)butan-2-ol hydrochloride (2:1), 150 mg of 7-[(methylsulfonyl)amino]-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid and 0.176 cm3 of triethylamine in 1.6 cm3 of anhydrous dimethylformamide are 64 mg of 1-hydroxy-7-azabenzotriazole then 90 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. The solution is kept stirring for 24 h at a temperature close to 20° C. 20 cm3 of water and 50 cm3 of ethyl acetate are added to the reaction medium. After decantation, the organic phase is washed with 20 cm3 of a saturated aqueous solution of ammonium chloride, five lots of 20 cm3 of water, 20 cm3 of saturated aqueous solution of sodium chloride, then 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 75 cm3 of ethyl acetate. The filtrate is concentrated to dryness under reduced pressure (5 kPa). 300 mg of N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-7-[(methylsulfonyl)amino]-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide are obtained in the form of a directly salified white powder.

Workup

  1. customclose to 20° C
  2. washAfter decantation, the organic phase is washed with 20 cm3 of a saturated aqueous solution of ammonium chloride, five lots of 20 cm3 of water, 20 cm3 of saturated aqueous solution of sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure (5 kPa)
  6. filtrationThe residual solution (around 3 cm3) is filtered through a pellet of 15 g of 40-63 μm silica
  7. washThe silica pellet is washed with 75 cm3 of ethyl acetate
  8. concentrationThe filtrate is concentrated to dryness under reduced pressure (5 kPa)

Sources & evidence

ORD record
ord-479f1b1a81b8466fa2d63f28071f0f6b
Source dataset
uspto-grants-2013_02
Patent number
US08372864B2

Reaction notes

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