Phosgene → HCID 86715383, compound

HRID 628170Notes

Reaction equation

HRID 628170 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 1N 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 1N 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-96a2999415254e3bb0452e7c467d021f
Source dataset
uspto-grants-2016_04
Patent number
US09309283B2

Reaction notes

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