1,2-Dichloroethane → HCID 131727177, compound

HRID 269999Notes

Reaction equation

HRID 269999 reaction equation
I[CH2:2][CH2:3][C@H:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[OH:5].[NH2:12][CH2:13][CH2:14][NH:15][S:16]([C:19]1[C:20]2[CH:21]=[CH:22][N:23]=[CH:24][C:25]=2[CH:26]=[C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:28]=1)(=[O:18])=[O:17].C(N(C(C)C)CC)(C)C.[Cl:44]CCCl>CN(C=O)C>[ClH:44].[ClH:44].[OH:5][C@@H:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:3][CH2:2][NH:12][CH2:13][CH2:14][NH:15][S:16]([C:19]1[C:20]2[CH:21]=[CH:22][N:23]=[CH:24][C:25]=2[CH:26]=[C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:28]=1)(=[O:18])=[O:17]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 112903567-Phenyl-isoquinoline-5-sulfonic acid (2-amino-ethyl)-amideHCID 14476875(R)-3-iodo-1-phenyl-1-propanol

Product 1

HCID 131727177HCID 131727177, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Add sodium iodide (4.29 g, 29 mmol) to a solution of (R)-(+)-3-chloro-1-phenyl-1-propanol (0.5 g, 2.93 mmol) in acetone (9.75 mL), and heat to reflux overnight. Cool and filter the suspension, then remove the volatiles under reduced pressure. Resuspend the residue in ether, filter and evaporate to afford (R)-3-iodo-1-phenyl-1-propanol (0.71 g). Add (R)-3-iodo-1-phenyl-1-propanol (0.1 g, 0.4 mmol) to a solution of 7-phenyl-isoquinoline -5-sulfonic acid (2-amino-ethyl)-amide (0.087 g, 0.27 mmol) in DMF (0.5 mL) and DCE (0.27 mL) containing diisopropylethylamine (0.094 mL, 0.53 mmol), and warm to 80° C. for 30 minutes. Cool to ambient temperature, and apply to a cation exchange resin cartridge. Wash with methanol, and elute product from the resin with 2M methanolic ammonia. Evaporate and purify the residue by silica gel chromatography using a methanol-methylene chloride gradient, followed by treatment with aqueous hydrochloric acid and lyophylization to afford the title compound. 1H NMR (DMSO): δ9.71(s, 1H), 9.00-8.82 (m, 3H), 8.80-8.73(m, 2H), 8.69 (d, J=1.8 Hz, 1H), 8.59 (d, J=6.2 Hz, 1H), 7.95 (dd, J1=1.5 Hz, J2=8.5 Hz, 2H), 7.62 (t, J=6.7 Hz, 2H), 7.53 (t, J=7.8 Hz, 1H), 7.38-7.29 (m, 4H), 7.28-7.21 (m, 1H), 5.50-4.67 (bs, 2H), 4.65 (dd, J1=4.5 Hz, J2=8.5 Hz, 1H), 3.23-3.10 (m, 2H), 3.06-2.86 (m, 4H), 2.00=−1.77(m, 2H). LCMS: m/z 462(M+H)+460(M−H)−.

Workup

  1. temperatureCool to ambient temperature
  2. washWash with methanol
  3. washelute product from the resin with 2M methanolic ammonia
  4. customEvaporate
  5. custompurify the residue by silica gel chromatography

Sources & evidence

ORD record
ord-64e7213f8af34e84a10fb1ac496027d7
Source dataset
uspto-grants-2008_11
Patent number
US07449477B2

Reaction notes

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