1,1-Dichloroethane → HCID 69732709, compound

HRID 432116Notes

Reaction equation

HRID 432116 reaction equation
[NH2:1][S:2]([C:5]1[CH:6]=[C:7]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[O:17][C@H:16]([CH2:21][N:22]([CH2:30][C@H:31]([O:38][Si](C(C)(C)C)(C)C)[C:32]2[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=2)C(=O)OC(C)(C)C)[CH2:15][CH2:14]3)[CH:8]=[CH:9][CH:10]=1)(=[O:4])=[O:3].CCN(CC)CC.[CH3:53][C:54]1[CH:59]=[CH:58][C:57]([N:60]=[C:61]=[O:62])=[CH:56][CH:55]=1.[Cl:63]C(Cl)C>>[ClH:63].[OH:38][C@H:31]([C:32]1[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=1)[CH2:30][NH:22][CH2:21][C@H:16]1[CH2:15][CH2:14][C:13]2[C:18](=[CH:19][CH:20]=[C:11]([C:7]3[CH:8]=[CH:9][CH:10]=[C:5]([S:2]([NH:1][C:61]([NH:60][C:57]4[CH:58]=[CH:59][C:54]([CH3:53])=[CH:55][CH:56]=4)=[O:62])(=[O:4])=[O:3])[CH:6]=3)[CH:12]=2)[O:17]1

Participants

5

Reactant 4

HCID 63651,1-DichloroethaneHCID 8471TriethylamineHCID 693254-Methylphenyl isocyanateHCID 91477717HCID 91477717, compound

Product 1

HCID 69732709HCID 69732709, compoundYield 50%

Procedure

To a stirred solution of Example 281 (45 mg) in dichloroethane (10 mL), were added Et3N (0.014 mL) and 4-methylphenyl isocyanate (0.013 mL). Stirring was continued at room temperature over a 2-3 hour period. The solvent was removed under reduced pressure. Crude product was purified by combiflash column chromatography to give the free base of the desired product (27 mg, 50% yield). This material was treated with HCl (4 M) in dioxane and stirred at room temperature overnight. The solvent was removed under reduced pressure to provide the crude product, which was purified by preparative HPLC to provide the title compound. MS [M+H]+573.21, Rf=0.68 (CH2Cl2:MeOH=50:50); H1 NMR (MeOH-d4, δ ppm): 2.25 (s, 3H), 2.85-3.08 (m, 2H), 3.38-3.67 (m, 6H), 4.50 4.54 (m, 1H), 5.45-5.47 (m, 1H), 7.04-7.07 (m, 4H), 7.24 (d, 2H, J=6.3 Hz), 7.40 (dd, 1H, J=6.3 Hz), 7.42-7.45 (m, 2H), 7.63 (t, 1H, J=6.0 Hz), 7.87 (d, 1H, J=6.0 Hz), 7.93 (d, 1H, J=6.0 Hz), 8.10-8.20 (m, 1H), 8.22 (s, 1H), 8.78-8.79 (m, 1H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customCrude product was purified by combiflash column chromatography

Sources & evidence

ORD record
ord-cb8162e0152244dc8901ebdb87102cfe
Source dataset
uspto-grants-2003_12
Patent number
US06660752B2

Reaction notes

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