4-Methylmorpholine → (S)-2-[(S)-4-(3-Chloro-4-trifluoromethoxy-phenylcarbamoyl)-3-methyl-2-oxo-piperazin-1-yl]-5-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-5-oxo-pentanoic acid methyl ester

HRID 2095572Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:26])[C@@H:4]([N:18]1[CH2:23][CH2:22][NH:21][C@@H:20]([CH3:24])[C:19]1=[O:25])[CH2:5][CH2:6][C:7]([N:9]1[CH2:16][CH2:15][C:12]2([CH2:14][CH2:13]2)[C@H:11]([OH:17])[CH2:10]1)=[O:8].CN1CCOCC1.[Cl:34][C:35]1[CH:40]=[C:39]([N:41]=[C:42]=[O:43])[CH:38]=[CH:37][C:36]=1[O:44][C:45]([F:48])([F:47])[F:46]>>[CH3:1][O:2][C:3](=[O:26])[C@@H:4]([N:18]1[CH2:23][CH2:22][N:21]([C:42](=[O:43])[NH:41][C:39]2[CH:38]=[CH:37][C:36]([O:44][C:45]([F:47])([F:48])[F:46])=[C:35]([Cl:34])[CH:40]=2)[C@@H:20]([CH3:24])[C:19]1=[O:25])[CH2:5][CH2:6][C:7]([N:9]1[CH2:16][CH2:15][C:12]2([CH2:14][CH2:13]2)[C@H:11]([OH:17])[CH2:10]1)=[O:8]

Participants

Reactant 3

HCID 79724-Methylmorpholine

HCID 15765405HCID 15765405, compound2×

HCID 67074057(S)-5-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-2-((S)-3-methyl-2-oxo-piperazin-1-yl)-5-oxo-pentanoic acid methyl ester2×

Product 1

HCID 58232194(S)-2-[(S)-4-(3-Chloro-4-trifluoromethoxy-phenylcarbamoyl)-3-methyl-2-oxo-piperazin-1-yl]-5-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-5-oxo-pentanoic acid methyl esterYield 67%

Procedure

In analogy to the procedure described in Example 30, (S)-5-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-2-((S)-3-methyl-2-oxo-piperazin-1-yl)-5-oxo-pentanoic acid methyl ester (intermediate 29) with 3 eq. of 4-methylmorpholine and 1.2 eq. of 2-chloro-4-isocyanato-1-trifluoromethoxy-benzene (intermediate 17) gave the titled compound in 67% yield as white foam. MS: 605.20 (MH+, Cl).

Sources & evidence

ORD record: ord-b27024efdc0741e89b527f17994e032d
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445674B2

Reaction notes

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