Acetic Acid → 11-(3-Chloro-4-fluorobenzyl)-4-pyrrolidin-1-yl-9-methoxy-2-methyl-3,4,5,6,12,13-hexahydro-2h[1,4]diazocino[2,1-a]-2,6-naphthyridine-1,8,10(11h)-trione

HRID 2066604Notes

Reaction equation

HRID 2066604 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:29]=[CH:30][C:31]=1[F:32])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([O:26][CH3:27])[C:10](=[O:25])[N:11]3[CH2:21][CH2:20][C:19](=O)[CH2:18][N:17]([CH3:23])[C:16](=[O:24])[C:12]3=2)[C:7]1=[O:28].[NH:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1.C(O)(=O)C.[BH4-].[Na+]>ClC(Cl)C.ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:29]=[CH:30][C:31]=1[F:32])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([O:26][CH3:27])[C:10](=[O:25])[N:11]3[CH2:21][CH2:20][CH:19]([N:33]4[CH2:37][CH2:36][CH2:35][CH2:34]4)[CH2:18][N:17]([CH3:23])[C:16](=[O:24])[C:12]3=2)[C:7]1=[O:28]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 31268PyrrolidineHCID 4311764Sodium borohydrideHCID 6725311811-(3-Chloro-4-fluorobenzyl)-9-methoxy-2-methyl-5,6,12,13-tetrahydro-2h[1,4]diazocino[2,1-a]-2,6-naphthyridine-1,4,8,10(3h, 11h)-tetrone

Product 1

HCID 6699793211-(3-Chloro-4-fluorobenzyl)-4-pyrrolidin-1-yl-9-methoxy-2-methyl-3,4,5,6,12,13-hexahydro-2h[1,4]diazocino[2,1-a]-2,6-naphthyridine-1,8,10(11h)-trione

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 11-(3-chloro-4-fluorobenzyl)-9-methoxy-2-methyl-5,6,12,13-tetrahydro-2H[1,4]diazocino[2,1-a]-2,6-naphthyridine-1,4,8,10(3H, 11H)-tetrone (30 mg, 0.06 mmol), molecular sieves (4A), pyrrolidine (23 mg, 0.32 mmol), and acetic acid (4 mg) in dichloroethane (1 mL) was heated at 80° C. for four hrs. The mixture was cooled to room temperature, treated with sodium borohydride (12 mg, 0.19 mmol), and stirred at room temperature for 30 minutes. The product mixture was diluted with dichloromethane, washed successively with aq sodium carbonate and brine. The organic extract was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum to provide the title compound. This material was used in the following step without further purification. ES MS M+1=517.3

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. washwashed successively with aq sodium carbonate and brine
  3. extractionThe organic extract
  4. dry with materialwas dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-93af4463d7444ed69e03d6b7a0333e77
Source dataset
uspto-grants-2012_10
Patent number
US08293731B2

Reaction notes

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