Dichloromethane → 8-[(3-bromophenyl)methyl]-4-(cyclohexylamino)-1-(3-fluorophenyl)-1,3,8-triazaspiro[4.5]dec-3-en-2-one

HRID 1641302Notes

Reaction equation

HRID 1641302 reaction equation
Cl.Cl.[CH:3]1([NH2+:9][C:10]2[C:14]3([CH2:19][CH2:18][NH2+:17][CH2:16][CH2:15]3)[N:13]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)[C:12](=[O:27])[N:11]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C(N(C(C)C)CC)(C)C.[Br:37][C:38]1[CH:39]=[C:40]([CH:43]=[CH:44][CH:45]=1)[CH:41]=O.C(Cl)Cl>ClCCCl>[Br:37][C:38]1[CH:39]=[C:40]([CH:43]=[CH:44][CH:45]=1)[CH2:41][N:17]1[CH2:16][CH2:15][C:14]2([N:13]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)[C:12](=[O:27])[N:11]=[C:10]2[NH:9][CH:3]2[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]2)[CH2:19][CH2:18]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 765833-BromobenzaldehydeHCID 81531DiisopropylethylamineHCID 866146104-(Cyclohexylammonio)-1-(3-fluorophenyl)-2-oxo-1,3-diaza-8-azoniaspiro[4.5]dec-3-ene dihydrochloride

Product 1

HCID 1785179678-[(3-bromophenyl)methyl]-4-(cyclohexylamino)-1-(3-fluorophenyl)-1,3,8-triazaspiro[4.5]dec-3-en-2-one

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

To a suspension of 600 mg (1.44 mmol) 4-(cyclohexylammonio)-1-(3-fluorophenyl)-2-oxo-1,3-diaza-8-azoniaspiro[4.5]dec-3-ene dihydrochloride, 376 μL (2.16 mmol) diisopropylethylamine, and 427 mg (2.01 mmol) triacetoxy sodium borohydride in 20 mL DCE was added dropwise a 4 mL DCE solution of 251 μL (2.16 mmol) 3-bromobenzaldehyde and the resulting heterogeneous mixture was stirred at rt overnight under a nitrogen atmosphere. The reaction mixture was treated with 50 mL CH2Cl2 and washed with 20 mL saturated NaHCO3 (aq), 20 mL brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification by automated flash chromatography (0-5% MeOH in CH2Cl2 over 25 m) afforded the product as a white solid. 1H NMR (CDCl3, 400 MHz): δ 7.75 (d, J=8.15 Hz, 1H), 7.45 (m, 2H), 7.36 (m, 1H), 7.22 (m, 1H), 7.15 (d, J=7.69 Hz, 1H), 7.02 (m, 3H), 3.97 (m, 1H), 3.50 (s, 2H), 2.76 (m, 2H), 2.43 (m, 2H), 2.09 (m, 4H), 1.95 (m, 2H), 1.75 (m, 2H), 1.68 (m, 1H), 1.41 (m, 2H), 1.23 (m, 3H). High resolution mass spec (FT/ICR): calc M+H=513.1660. found 513.1697

Workup

  1. washwashed with 20 mL saturated NaHCO3 (aq), 20 mL brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by automated flash chromatography (0-5% MeOH in CH2Cl2 over 25 m)

Sources & evidence

ORD record
ord-ab8862322a9f4608963e3a0338edbf81
Source dataset
uspto-grants-2012_02
Patent number
US08114887B2

Reaction notes

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