N-bromobutanimide → HCID 86649133, compound

HRID 1471062Notes

Reaction equation

HRID 1471062 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([C@:19]4([C:35](=[O:37])[NH2:36])[CH2:23][CH2:22][CH2:21][N:20]4[C:24](=[O:34])[C@@H:25]([NH:29][C:30](=[O:33])[O:31][CH3:32])[CH:26]([CH3:28])[CH3:27])=[CH:15][CH:14]=3)=[CH:11][CH:10]=[C:9]2[C:38]2[CH:43]=[CH:42][C:41]([C@:44]3([C:60](=[O:62])[NH2:61])[CH2:48][CH2:47][CH2:46][N:45]3[C:49](=[O:59])[C@@H:50]([NH:54][C:55](=[O:58])[O:56][CH3:57])[CH:51]([CH3:53])[CH3:52])=[CH:40][CH:39]=2)=[CH:4][CH:3]=1.[Br:63]N1C(=O)CCC1=O>C(Cl)Cl>[Br:63][C:10]1[CH:11]=[C:12]([C:13]2[CH:18]=[CH:17][C:16]([C@:19]3([C:35](=[O:37])[NH2:36])[CH2:23][CH2:22][CH2:21][N:20]3[C:24](=[O:34])[C@@H:25]([NH:29][C:30](=[O:33])[O:31][CH3:32])[CH:26]([CH3:28])[CH3:27])=[CH:15][CH:14]=2)[N:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[C:9]=1[C:38]1[CH:39]=[CH:40][C:41]([C@:44]2([C:60](=[O:62])[NH2:61])[CH2:48][CH2:47][CH2:46][N:45]2[C:49](=[O:59])[C@@H:50]([NH:54][C:55](=[O:58])[O:56][CH3:57])[CH:51]([CH3:52])[CH3:53])=[CH:42][CH:43]=1

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 86649134HCID 86649134, compound

Product 1

HCID 86649133HCID 86649133, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of the product from Example 51 (455 mg, 0.534 mmol) in CH2Cl2 (2.7 mL) was added a mixture of 1-bromopyrrolidine-2,5-dione (95 mg, 0.534 mmol) in CH2Cl2 (2.7 mL). The mixture was stirred overnight at room temperature then concentrated under reduced pressure and triturated with diethyl ether to provide a mixture of compounds that was subjected to reverse phase HPLC purification eluted with a gradient of 60-100% MeOH in 10 mM ammonium acetate to afford the title compound (84 mg, 17% yield). 1H NMR (free base) (400 MHz, DMSO-D6) δ 10.06 (s, 1H), 10.02 (s, 1H), 7.46 (d, J=8.7, 2H), 7.41 (d, J=8.7, 2H), 7.30 (d, J=7.7, 2H), 7.15-7.03 (m, 6H), 6.98 (d, J=8.7, 2H), 6.53 (s, 1H), 4.45-4.33 (m, 2H), 4.01 (t, J=7.7, 2H), 3.85-3.73 (m, 2H), 3.66-3.54 (m, 2H), 3.51 (s, 6H), 2.20-2.05 (m, 2H), 2.03-1.77 (m, 8H), 0.97-0.79 (m, 12H). MS (ESI; M+H) m/z=933.

Workup

  1. additionwas added
  2. concentrationthen concentrated under reduced pressure
  3. customtriturated with diethyl ether
  4. customto provide
  5. additiona mixture of compounds that
  6. customphase HPLC purification
  7. washeluted with a gradient of 60-100% MeOH in 10 mM ammonium acetate

Sources & evidence

ORD record
ord-53754d915847458b814dd1fc6c3cbd10
Source dataset
uspto-grants-2015_04
Patent number
US09006387B2

Reaction notes

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