4-Methylmorpholine → (R)-4-[3-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-propyl]-2-methyl-5-oxo-[1,4]diazepane-1-carboxylic acid (3-chloro-2-fluoro-phenyl)-amide

HRID 655574Notes

Reaction equation

HRID 655574 reaction equation
Cl.Cl.[OH:3][C@@H:4]1[CH2:11][N:10]([CH2:12][CH2:13][CH2:14][N:15]2[C:21](=[O:22])[CH2:20][CH2:19][NH:18][C@H:17]([CH3:23])[CH2:16]2)[CH2:9][CH2:8][C:5]21[CH2:7][CH2:6]2.[Cl:24][C:25]1[C:26]([F:34])=[C:27]([N:31]=[C:32]=[O:33])[CH:28]=[CH:29][CH:30]=1.[N-]=C=O.CN1CCOCC1>>[Cl:24][C:25]1[C:26]([F:34])=[C:27]([NH:31][C:32]([N:18]2[CH2:19][CH2:20][C:21](=[O:22])[N:15]([CH2:14][CH2:13][CH2:12][N:10]3[CH2:9][CH2:8][C:5]4([CH2:6][CH2:7]4)[C@H:4]([OH:3])[CH2:11]3)[CH2:16][C@H:17]2[CH3:23])=[O:33])[CH:28]=[CH:29][CH:30]=1

Participants

5

Reactant 4

HCID 79724-MethylmorpholineHCID 105034IsocyanateHCID 40926241-Chloro-2-fluoro-3-isocyanatobenzeneHCID 67080697(R)-4-[3-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-propyl]-2-methyl-[1,4]diazepan-5-one dihydrochloride

Product 1

HCID 59149926(R)-4-[3-((S)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-propyl]-2-methyl-5-oxo-[1,4]diazepane-1-carboxylic acid (3-chloro-2-fluoro-phenyl)-amide

Procedure

In analogy to the procedure described in example 58F, (R)-4-[3-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-propyl]-2-methyl-[1,4]diazepan-5-one dihydrochloride (example 58E) and 3-chloro-2-fluorophenyl isocyanate (but with 2.1 eq. of isocyanate and 5 eq. of 4-methylmorpholine) gave after extraction with sat. aq. sodium hydrogencarbonate solution/1 M aq. sodium hydroxide solution and dichloromethane (3 times) 0.016 g (12%) of the title compound as white foam. MS: 467.2 (MH+, 1Cl).

Workup

  1. customgave
  2. extractionafter extraction with sat. aq. sodium hydrogencarbonate solution/1 M aq. sodium hydroxide solution and dichloromethane (3 times) 0.016 g (12%) of the title compound as white foam

Sources & evidence

ORD record
ord-cf1fa3a55ffb43349fb3259f3ac0611f
Source dataset
uspto-grants-2011_12
Patent number
US08071586B2

Reaction notes

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