Chlorosuccinimide → HCID 10293010, compound

HRID 2416678Notes

Reaction equation

HRID 2416678 reaction equation
[C:1]([C:3]1[CH:25]=[CH:24][C:6]2[NH:7][C:8]3[N:9]=[CH:10][CH:11]=[CH:12][C:13]=3[C:14]([CH2:19][O:20][CH:21]([CH3:23])[CH3:22])([C:15]([F:18])([F:17])[CH3:16])[C:5]=2[CH:4]=1)#[N:2].CC(O)C.CC#N.C1C(=O)N([Cl:40])C(=O)C1>CCOC(C)=O.CCCCCC>[Cl:40][C:11]1[CH:10]=[N:9][C:8]2[NH:7][C:6]3[CH:24]=[CH:25][C:3]([C:1]#[N:2])=[CH:4][C:5]=3[C:14]([CH2:19][O:20][CH:21]([CH3:22])[CH3:23])([C:15]([F:17])([F:18])[CH3:16])[C:13]=2[CH:12]=1

Participants

5

Reactant 3

HCID 31398ChlorosuccinimideHCID 10268983HCID 10268983, compoundHCID 21921005Acetonitrile 2-propanol

Product 1

HCID 10293010HCID 10293010, compoundYield 84.1%

Reagents, catalysts & solvents 1

HCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a stirred solution of 7-cyano-5-isopropoxymethyl-5-(1,1-difluoroethyl)-5,10-dihydrobenzo[b][1,8]naphthyridine (22)(2.184 g, 6.361 mmol) in anhydrous 1:4 i-PrOH-MeCN (35 mL) at room temperature was added NCS (1.040 g, 7.633 mmol). The reaction mixture was heated to reflux for 2 h 40 min. The reaction was quenched with saturated aqueous NaHCO3 (100 mL), and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. Flash chromatography (20%-30% EtOAc-Hexane) afforded 23 (2.021 g, 84% yield) as a pale yellow solid: m.p. 79-81° C.; low resolution mass spectrum (ESI) m/z 378.3 [(M+H)+ calcd for C19H19ClF2N3O: 378.12].

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 2 h 40 min
  3. customThe reaction was quenched with saturated aqueous NaHCO3 (100 mL)
  4. extractionextracted with EtOAc (2×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d670e1e6106f4cd990708d61929b7d5d
Source dataset
uspto-grants-2004_11
Patent number
US06825210B2

Reaction notes

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