3-Fluoroazetidine → HCID 90333604, compound

HRID 595735

Reaction equation

HRID 595735 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[CH2:8][CH:7]([CH2:12][CH:13]=O)[N:6]3[C:15]4[CH:16]=[CH:17][CH:18]=[C:19]([F:22])[C:20]=4[CH:21]=[C:5]3[C:4]=2[N:3]=1.[F:23][CH:24]1[CH2:27][NH:26][CH2:25]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[CH2:8][CH:7]([CH2:12][CH2:13][N:26]3[CH2:27][CH:24]([F:23])[CH2:25]3)[N:6]3[C:15]4[CH:16]=[CH:17][CH:18]=[C:19]([F:22])[C:20]=4[CH:21]=[C:5]3[C:4]=2[N:3]=1

Participants

5

Reactant 3

HCID 36035423-FluoroazetidineHCID 5049666Sodium triacetoxyborohydrideHCID 90333623HCID 90333623, compound

Product 1

HCID 90333604HCID 90333604, compoundYield 43.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-6-yl)acetaldehyde (200 mg, 0.617 mmol) and 3-fluoroazetidine (95 mg, 1.23 mmol) in DCM (4 mL) was stirred at room temperature for 30 minutes under N2. Then Na(OAc)3BH (50 mg) was added to the mixture, and the mixture was stirred at room temperature for 1 hour. After dilution with water (30 mL) and extraction with EA (20 mL×3), the organic layer was washed with brine (30 mL*3), dried over Na2SO4 and concentrated. The residue was purified by column chromatography (PE:EA=1:1) to afford the desired product of 2-chloro-11-fluoro-6-(2-(3-fluoroazetidin-1-yl)ethyl)-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (100 mg, yield: 43%). 1H-NMR (CDCl3, 400 MHz) δ 7.44 (d, J=8.0 Hz, 1H), 7.3 (s, 1H), 7.16 (d, J=8.0 Hz, 1H), 7.10 (t, J=4.8 Hz, J=2.7 Hz, 2H), 6.69˜6.74 (m, 1H), 5.11˜5.14 (m, 0.5H), 4.97˜4.50 (m, 0.5H), 4.87 (t, J=4.8 Hz, 1H), 3.57 (d, J=6.8 Hz, 1H), 3.33˜3.39 (m, 1H), 2.95˜3.06 (m, 2H), 2.2˜72.38 (m, 1H). MS (M+H)+: 374/376.

Workup

  1. stirringthe mixture was stirred at room temperature for 1 hour
  2. extractionAfter dilution with water (30 mL) and extraction with EA (20 mL×3)
  3. washthe organic layer was washed with brine (30 mL*3)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (PE:EA=1:1)

Sources & evidence

ORD record
ord-1fed303d4b3f4705afea55f1a59cb280
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Linked notes

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