Dichloromethane → HCID 178502424, compound

HRID 2364848Notes

Reaction equation

HRID 2364848 reaction equation
[Cl:1]N1C(=O)CCC1=O.[CH3:9][O:10][C:11](=[O:79])[NH:12][C@@H:13]([CH:76]([CH3:78])[CH3:77])[C:14]([N:16]1[CH2:20][CH2:19][CH2:18][C@H:17]1[C:21]1[NH:22][C:23]([C:26]2[CH:31]=[CH:30][C:29]([C@H:32]3[CH2:36][CH2:35][C@H:34]([C:37]4[CH:42]=[CH:41][C:40]([C:43]5[NH:47][C:46]([C@@H:48]6[CH2:52][CH2:51][CH2:50][N:49]6[C:53](=[O:63])[C@@H:54]([NH:58][C:59]([O:61][CH3:62])=[O:60])[CH:55]([CH3:57])[CH3:56])=[N:45]C=5)=[CH:39][CH:38]=4)[N:33]3[C:64]3[CH:69]=[CH:68][C:67]([CH:70]4[CH2:75][CH2:74][CH2:73][CH2:72][CH2:71]4)=[CH:66][CH:65]=3)=[CH:28][CH:27]=2)=[CH:24][N:25]=1)=[O:15].Cl[CH2:81][Cl:82]>>[CH3:9][O:10][C:11](=[O:79])[NH:12][C@@H:13]([CH:76]([CH3:78])[CH3:77])[C:14]([N:16]1[CH2:20][CH2:19][CH2:18][C@H:17]1[C:21]1[NH:22][C:23]([C:26]2[CH:31]=[CH:30][C:29]([C@H:32]3[CH2:36][CH2:35][C@H:34]([C:37]4[CH:42]=[CH:41][C:40]([C:43]5[NH:47][C:46]([C@@H:48]6[CH2:52][CH2:51][CH2:50][N:49]6[C:53](=[O:63])[C@@H:54]([NH:58][C:59]([O:61][CH3:62])=[O:60])[CH:55]([CH3:57])[CH3:56])=[N:45][C:81]=5[Cl:82])=[CH:39][CH:38]=4)[N:33]3[C:64]3[CH:69]=[CH:68][C:67]([CH:70]4[CH2:75][CH2:74][CH2:73][CH2:72][CH2:71]4)=[CH:66][CH:65]=3)=[CH:28][CH:27]=2)=[C:24]([Cl:1])[N:25]=1)=[O:15]

Participants

4

Reactant 3

HCID 6344Dichloromethane2×HCID 31398ChlorosuccinimideHCID 59617042HCID 59617042, compound

Product 1

HCID 178502424HCID 178502424, compoundYield 13%

Procedure

N-Chlorosuccinimide (0.046 g, 0.342 mmol) was added to a solution of the product from Example 128 (0.1435 g, 0.149 mmol) in dichloromethane (7 mL) and stirred at ambient temperature for 17 hours. The reaction was diluted with dichloromethane and washed with sat aq NaHCO3 (2×) and concentrated. The residue was purified by flash chromatography (silica gel, MeOH/dichloromethane) then by prep HPLC to afford the title compound (20.4 mg, 13%). 1H NMR (free base) (400 MHz, DMSO-D6) δ 0.94-0.73 (m, 12H), 1.39-0.99 (m, 8H), 1.75-1.41 (m, 6H), 2.27-1.77 (m, 12H), 3.53 (s, 6H), 3.86-3.66 (m, 3H), 4.08-3.96 (m, 2H), 5.11-4.89 (m, 2H), 5.30-5.12 (m, 1H), 5.55-5.33 (m, 1H), 6.21 (d, J=8.7, 1H), 6.88-6.67 (m, 2H), 6.94 (dd, J=4.3, 8.4, 1H), 7.42-7.02 (m, 6H), 7.56-7.42 (m, 3H), 7.61 (t, J=8.5, 1H), 11.68 (d, J=10.7, 1H), 12.49-12.26 (m, 1H). MS (ESI) m/z 1034 (M+H)+.

Workup

  1. washwashed with sat aq NaHCO3 (2×)
  2. concentrationconcentrated
  3. customThe residue was purified by flash chromatography (silica gel, MeOH/dichloromethane)

Sources & evidence

ORD record
ord-72f006149806456484591b67c932f305
Source dataset
uspto-grants-2014_04
Patent number
US08691938B2

Reaction notes

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