Phosgene → HCID 86715383, compound

HRID 630639Notes

Reaction equation

HRID 630639 reaction equation
[OH:1][C@@:2]([CH3:53])([C:5](=[O:52])[C@@H:6]([NH:11][C:12]([C@@H:14]([NH:22][C:23](=[O:51])[C@@H:24]([NH:29][C:30](=[O:50])[C@@H:31]([NH:40][C:41](=[O:49])[CH2:42][N:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1)[CH2:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:25][CH:26]([CH3:28])[CH3:27])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])[CH2:7][CH:8]([CH3:10])[CH3:9])[CH2:3][I:4].[C:54](Cl)(Cl)=[O:55].[CH2:58]([OH:61])[C:59]#[CH:60]>ClCCl.CN(C1C=CN=CC=1)C>[C:54](=[O:55])([O:61][CH2:58][C:59]#[CH:60])[O:1][C@:2]([CH3:53])([CH2:3][I:4])[C:5](=[O:52])[C@H:6]([CH2:7][CH:8]([CH3:9])[CH3:10])[NH:11][C:12](=[O:13])[C@H:14]([CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[NH:22][C:23](=[O:51])[C@H:24]([CH2:25][CH:26]([CH3:27])[CH3:28])[NH:29][C:30](=[O:50])[C@H:31]([CH2:32][CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[NH:40][C:41](=[O:49])[CH2:42][N:43]1[CH2:44][CH2:45][O:46][CH2:47][CH2:48]1

Participants

6

Reactant 3

HCID 6371PhosgeneHCID 7859Propargyl alcoholHCID 86715379HCID 86715379, compound

Product 1

HCID 86715383HCID 86715383, compoundYield 17.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

(2S)—N—((S)-1-((2S,4S)-2-hydroxy-1-iodo-2,6-dimethyl-3-oxoheptan-4-ylcarbamoyl)-2-phenylethyl)-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)-4-methylpentanamide (1.18 g, 1.39 mmol) was dissolved in dichloromethane. DMAP (1.92 g, 13.9 mmol) was added and the mixture cooled to 0° C. Phosgene solution (20% in toluene, 3.75 mL, 5.52 mmol) was added dropwise and the reaction stirred at 0° C. for 30 minutes. Propargyl alcohol (0.802 ml, 13.9 mmol) was added and the mixture stirred at room temperature for 16 hours. The reaction was diluted with 200 mL dichloromethane, washed with 1 N HCl (50 ml) and brine (50 mL), dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by prep HPLC to afford 230 mg of white solid. 1H NMR (DMSO-d6): δ 8.37 (d, J=8.5 Hz, 1H), 8.18 (s, 1H), 8.12 (d, J=8.0 Hz, 1H), 8.03 (d, J=8.5 Hz, 1H), 7.88 (d, J=8.5 Hz, 1H), 7.28-7.08 (m, 10H), 5.19 (s, 2H), 4.89-4.83 (m, 1H), 4.57-4.51 (m, 4H), 4.37-4.28 (m, 2H), 3.87-3.79 (m, 4H), 3.65-3.31 (m, 793H), 2.96-2.90 (m, 4H), 2.80-2.76 (m, 1H), 2.50-2.42 (m, 6H), 1.89-75 (m, 2H), 1.58-1.30 (m, 9H). 0.86-0.74 (m, 12H).

Workup

  1. stirringthe mixture stirred at room temperature for 16 hours
  2. washwashed with 1 N HCl (50 ml) and brine (50 mL)
  3. dry with materialdried over anhydrous MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by prep HPLC

Sources & evidence

ORD record
ord-bd72f202c0634a18a9fdf771af3df415
Source dataset
uspto-grants-2016_04
Patent number
US09315542B2

Reaction notes

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