1,2-Dichloroethane → 3-((3S,9aS)-8-(2-(5-(1H-tetrazol-1-yl)pyridin-2-yl)acetyl)-octahydropyrazino [2,1-c][1,4]oxazin-3-yl)-6-fluoro-2-methylbenzonitrile

HRID 1502174Notes

Reaction equation

HRID 1502174 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1[C:14]([C:15]#[N:16])=[C:13]([CH3:17])[C:12]([C@@H:18]2[O:23][CH2:22][C@@H:21]3[CH2:24][NH:25][CH2:26][CH2:27][N:20]3[CH2:19]2)=[CH:11][CH:10]=1.[N:28]1([C:33]2[CH:34]=[CH:35][C:36]([CH2:39][C:40](O)=[O:41])=[N:37][CH:38]=2)[CH:32]=[N:31][N:30]=[N:29]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[Cl-].[Na+].O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[N:28]1([C:33]2[CH:34]=[CH:35][C:36]([CH2:39][C:40]([N:25]3[CH2:26][CH2:27][N:20]4[C@H:21]([CH2:22][O:23][C@@H:18]([C:12]5[C:13]([CH3:17])=[C:14]([C:9]([F:8])=[CH:10][CH:11]=5)[C:15]#[N:16])[CH2:19]4)[CH2:24]3)=[O:41])=[N:37][CH:38]=2)[CH:32]=[N:31][N:30]=[N:29]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 675176762-(5-(1H-tetrazol-1-yl)pyridin-2-yl)acetic acidHCID 867270906-Fluoro-2-methyl-3-((3S,9aS)-octahydropyrazino[2,1-c][1,4]oxazin-3-yl)benzonitrile 2,2,2-trifluoroacetateHCID 129703874Sodium hydrogencarbonate brine

Product 1

HCID 716039183-((3S,9aS)-8-(2-(5-(1H-tetrazol-1-yl)pyridin-2-yl)acetyl)-octahydropyrazino [2,1-c][1,4]oxazin-3-yl)-6-fluoro-2-methylbenzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

6-Fluoro-2-methyl-3-((3S,9aS)-octahydropyrazino[2,1-c][1,4]oxazin-3-yl)benzonitrile 2,2,2-trifluoroacetate (1.06 g, 2.71 mmol) was suspended in DCM (20 mL) and TEA (1.13 ml, 8.13 mmol) was added. The mixture was stirred for 5 min and then 2-(5-(1H-tetrazol-1-yl)pyridin-2-yl)acetic acid (0.555 g, 2.71 mmol), HOBT (0.623 g, 4.07 mmol) and EDC (1.039 g, 5.42 mmol) were added and the mixture was stirred for 4 h. The reaction mixture was poured into brine/NaHCO3 mixture. The DCM layer was separated and dried over Na2SO4, then was filtered and concentrated. The residue was purified by chromatography using a 120 g ISCO Redisep column eluting with a 5% (NH4OH: MeOH 1:9)/95% DCM solvent system to yield 3-((3S,9aS)-8-(2-(5-(1H-tetrazol-1-yl)pyridin-2-yl)acetyl)-octahydropyrazino[2,1-c][1,4]oxazin-3-yl)-6-fluoro-2-methylbenzonitrile: LC-MS: M+1=463.

Workup

  1. stirringthe mixture was stirred for 4 h
  2. customThe DCM layer was separated
  3. dry with materialdried over Na2SO4
  4. filtrationwas filtered
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography
  7. washeluting with a 5% (NH4OH: MeOH 1:9)/95% DCM solvent system

Sources & evidence

ORD record
ord-5653d7c941fa4729897b6a78d601e61e
Source dataset
uspto-grants-2015_12
Patent number
US09206199B2

Reaction notes

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