Hydrochloric Acid → HCID 86607400, compound

HRID 1178899Notes

Reaction equation

HRID 1178899 reaction equation
[ClH:1].[C:2]([N:6]1[CH2:10][C@@H:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[F:18])[C@H:8]([C:19](O)=[O:20])[CH2:7]1)([CH3:5])([CH3:4])[CH3:3].[Cl-].[CH:23]1([C:29]2([CH2:37][S:38][CH3:39])[CH2:35][CH:34]3[NH2+:36][CH:31]([CH2:32][CH2:33]3)[CH2:30]2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.Cl>ClCCl.CCOCC>[Cl-:1].[C:2]([NH+:6]1[CH2:10][C@@H:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[F:18])[C@@H:8]([C:19]([N:36]2[CH:34]3[CH2:33][CH2:32][CH:31]2[CH2:30][C:29]([CH:23]2[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]2)([CH2:37][S:38][CH3:39])[CH2:35]3)=[O:20])[CH2:7]1)([CH3:4])([CH3:3])[CH3:5]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67212109(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid hydrochlorideHCID 68526195HCID 68526195, compound

Product 1

HCID 86607400HCID 86607400, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (3R,4S)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid (1-10) (0.170 g, 0.601 mmol) in dichloromethane (5.0 mL) was added 3-cyclohexyl-3-[(methylthio)methyl]-8-azoniabicyclo[3.2.1]octane chloride (3-6) (0.174 g, 0.601 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 0.173 g, 0.901 mmol), 1-hydroxyl-7-azabenzotriazole (HOAT, 0.082 g, 0.603 mmol), and diisopropylethylamine (0.105 mL, 0.601 mmol). The mixture was stirred at room temperature overnight, diluted with methylene chloride, washed with water and a saturated aqueous solution of NaHCO3. The organic phase was dried over anhydrous MgSO4, filtered, and concentrated. Purification of the crude residue by preparative TLC (90% methylene chloride, 9% methanol, 1% of a 40% of NH4OH aqueous soltion as eluent), followed by the addition of one equivalent HCl in ether to afford (3-7) as white solid (m/z (ES) 519 (MH+)).

Workup

  1. washwashed with water
  2. dry with materialThe organic phase was dried over anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification of the crude residue by preparative TLC (90% methylene chloride, 9% methanol, 1% of a 40% of NH4OH aqueous soltion as eluent),

Sources & evidence

ORD record
ord-87ec9c0272874ac4b7a8a08fbb72f8a0
Source dataset
uspto-grants-2007_10
Patent number
US07276520B2

Reaction notes

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