Diisopropylethylamine → HCID 90372996, compound

HRID 930310Notes

Reaction equation

HRID 930310 reaction equation
[NH2:1][C@@:2]([C:11]1[C:16]([F:17])=[CH:15][CH:14]=[C:13]([Br:18])[N:12]=1)([CH3:10])[CH2:3][C@H:4]([OH:9])[C:5]([F:8])([F:7])[F:6].[N+:19]([C:22]1[CH:32]=[CH:31][C:25]([C:26]([N:28]=[C:29]=S)=[O:27])=[CH:24][CH:23]=1)([O-:21])=[O:20].Cl.C(N=C=NCCCN(C)C)C.C(N(C(C)C)C(C)C)C>CC#N>[Br:18][C:13]1[N:12]=[C:11]([C@:2]2([CH3:10])[CH2:3][C@H:4]([C:5]([F:6])([F:7])[F:8])[O:9][C:29]([NH:28][C:26](=[O:27])[C:25]3[CH:24]=[CH:23][C:22]([N+:19]([O-:21])=[O:20])=[CH:32][CH:31]=3)=[N:1]2)[C:16]([F:17])=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1413984-Nitrobenzoyl isothiocyanate2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 90372889HCID 90372889, compound

Product 1

HCID 90372996HCID 90372996, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (2R,4S)-4-amino-4-(6-bromo-3-fluoropyridin-2-yl)-1,1,1-trifluoropentan-2-ol (7f, 0.183 g, 0.553 mmol) in MeCN (3 mL) was added 4-nitrobenzoyl isothiocyanate (Matrix, 0.150 g, 0.719 mmol). The mixture was stirred at room temperature for 30 min. Additional 4-nitrobenzoyl isothiocyanate (30 mg) was added and the reaction was allowed to stir for additional 20 min. N1-((Ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (Aldrich, 0.170 g, 0.884 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.241 mL, 1.382 mmol) was added and the reaction mixture was heated to 70° C. for 1 h. The reaction mixture was partitioned between water and EtOAc. The organic layer was separated washed with brine, and dried over sodium sulfate. The filtrate was concentrated under reduced pressure and the crude material was purified by silica gel chromatography (0-60% EtOAc/hexanes) to obtain the title compound as an off-white solid. MS m/z=505/507 [M]+/[M+2]+. Calculated: 505.2

Workup

  1. stirringto stir for additional 20 min
  2. temperaturethe reaction mixture was heated to 70° C. for 1 h
  3. customThe reaction mixture was partitioned between water and EtOAc
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe crude material was purified by silica gel chromatography (0-60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-008e1ef6a3bc476d8eb6f335718254bc
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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