2,6-Lutidine → HCID 24855988, compound

HRID 388539Notes

Reaction equation

HRID 388539 reaction equation
[CH2:1]([N:8]1[CH2:26][CH2:25][C:11]2([N:15]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[C:14](=[O:23])[CH2:13][C:12]2=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br.Br[CH2:29][CH2:30][CH2:31][NH2:32].N1C(C)=CC=CC=1C>C(O)(C)C>[CH2:1]([N:8]1[CH2:26][CH2:25][C:11]2([C:12]3[NH:32][CH2:31][CH2:30][CH2:29][C:13]=3[C:14](=[O:23])[N:15]2[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 787013-Bromopropylamine hydrobromideHCID 59252699HCID 59252699, compound

Product 1

HCID 24855988HCID 24855988, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 8-benzyl-1-(3-fluorophenyl)-1,8-diazaspiro[4.5]decane-2,4-dione (Intermediate 1A.4-1, 300 mg, 0.85 mmol) in isopropanol (4.3 ml) were added 3-bromopropylamine hydrobromide (205 mg, 0.94 mmol) and 2,6-lutidine (0.22 ml, 1.87 mmol). The reaction vessel was sealed and heated at 80° C. for 3 days. The reaction was concentrated in vacuo and partitioned between dichloromethane and 1N NaOH. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified via flash chromatography (silica, 0-5% methanol (10% NH4OH)/dichloromethane) to yield 1-benzyl-6′-(3-fluorophenyl)-1′,2′,3′,4′-tetrahydrospiro[piperidine-4,7′-pyrrolo[3,4-b]pyridin]-5′(6′H)-one. LCMS (M+H) 392.1. 1H NMR (400 MHz, CDCl3) δ 7.28 (m, 6H), 7.03 (td, J=8.2, 2.0 Hz, 1H), 6.97 (d, J=7.9 Hz, 1H), 6.92 (dt, J=9.9, 2.1 Hz, 1H), 3.46 (s, 2H), 3.33 (m, 2H), 2.52 (t, J=6.1 Hz, 41H), 2.33 (t, J=6.2 Hz, 2H), 2.06 (quint, J=6.9 Hz, 2H), 1.84 (m, 4H).

Workup

  1. customThe reaction vessel was sealed
  2. concentrationThe reaction was concentrated in vacuo
  3. custompartitioned between dichloromethane and 1N NaOH
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified via flash chromatography (silica, 0-5% methanol (10% NH4OH)/dichloromethane)

Sources & evidence

ORD record
ord-f38e63ceaaf4455296d0b6e404109f2e
Source dataset
uspto-grants-2013_02
Patent number
US08377954B2

Reaction notes

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