(2S)-2-(2-(((Benzylcarbamoyl)amino)(prop-2-en-1-yl)amino)acetamido)-3-(4-(benzyloxy)-2-fluorophenyl)-N-(2,2-diethoxyethyl)-N-((6-fluoropyridin-2-yl)methyl)propanamide → (6S,9aS)-N-Benzyl-6-((4-(benzyloxy)-2-fluorophenyl)methyl)-8-((6-fluoropyridin-2-yl)methyl)-4,7-dioxo-2-(prop-2-en-1-yl)-octahydro-1H-pyrazino[2,1-c][1,2,4]triazine-1-carboxamide

HRID 707495Notes

Reaction equation

HRID 707495 reaction equation
[CH2:1]([NH:8][C:9]([NH:11][N:12]([CH2:53][CH:54]=[CH2:55])[CH2:13][C:14]([NH:16][C@@H:17]([CH2:37][C:38]1[CH:43]=[CH:42][C:41]([O:44][CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)=[CH:40][C:39]=1[F:52])[C:18]([N:20]([CH2:29][CH:30](OCC)OCC)[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[N:23]=1)=[O:19])=[O:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(O)=O>[CH2:1]([NH:8][C:9]([N:11]1[C@H:30]2[CH2:29][N:20]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[N:23]=3)[C:18](=[O:19])[C@H:17]([CH2:37][C:38]3[CH:43]=[CH:42][C:41]([O:44][CH2:45][C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=4)=[CH:40][C:39]=3[F:52])[N:16]2[C:14](=[O:15])[CH2:13][N:12]1[CH2:53][CH:54]=[CH2:55])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 1

HCID 118162453(2S)-2-(2-(((Benzylcarbamoyl)amino)(prop-2-en-1-yl)amino)acetamido)-3-(4-(benzyloxy)-2-fluorophenyl)-N-(2,2-diethoxyethyl)-N-((6-fluoropyridin-2-yl)methyl)propanamide

Product 1

HCID 118162441(6S,9aS)-N-Benzyl-6-((4-(benzyloxy)-2-fluorophenyl)methyl)-8-((6-fluoropyridin-2-yl)methyl)-4,7-dioxo-2-(prop-2-en-1-yl)-octahydro-1H-pyrazino[2,1-c][1,2,4]triazine-1-carboxamideYield 80%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

A mixed solution of (2S)-2-(2-(((benzylcarbamoyl)amino)(prop-2-en-1-yl)amino)acetamido)-3-(4-(benzyloxy)-2-fluorophenyl)-N-(2,2-diethoxyethyl)-N-((6-fluoropyridin-2-yl)methyl)propanamide (7.28 g, 9.48 mmol) described in Production Example 1-1-4 and formic acid (50 mL) was stirred at room temperature for 15 hours and 15 minutes. The reaction mixture was concentrated under a reduced pressure, an aqueous ammonia solution was added to the residue, and the resultant solution was extracted with ethyl acetate. An organic layer was dried over anhydrous magnesium sulfate and then filtrated. The solvent was evaporated under a reduced pressure, and the resultant residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1) to give the title compound (5.04 g, yield: 80%).

Workup

  1. concentrationThe reaction mixture was concentrated under a reduced pressure
  2. additionan aqueous ammonia solution was added to the residue
  3. extractionthe resultant solution was extracted with ethyl acetate
  4. dry with materialAn organic layer was dried over anhydrous magnesium sulfate
  5. filtrationfiltrated
  6. customThe solvent was evaporated under a reduced pressure
  7. customthe resultant residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-6797cc378e274526a6b2fb60fb75f704
Source dataset
uspto-grants-2015_11
Patent number
US09174998B2

Reaction notes

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