Diisopropylethylamine → HCID 58576912, compound

HRID 511148Notes

Reaction equation

HRID 511148 reaction equation
[Li+].[F:2][C:3]([F:23])([F:22])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][C:19]([O-])=[O:20])[CH2:12][CH2:11]2)=[CH:6][CH:5]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.CN(C)C(ON1C2C=CC=CC=2N=N1)=[N+](C)C.Cl.[Cl:58][C:59]1[CH:66]=[C:65]([NH:67][CH:68]2[CH2:73][CH2:72][NH:71][CH2:70][CH2:69]2)[CH:64]=[CH:63][C:60]=1[C:61]#[N:62]>CN(C)C=O.ClCCl.O1CCCC1>[Cl:58][C:59]1[CH:66]=[C:65]([NH:67][CH:68]2[CH2:73][CH2:72][N:71]([C:19](=[O:20])[CH2:18][CH2:17][CH2:16][N:13]3[CH2:12][CH2:11][N:10]([C:7]4[CH:8]=[CH:9][C:4]([C:3]([F:22])([F:2])[F:23])=[CH:5][CH:6]=4)[CH2:15][CH2:14]3)[CH2:70][CH2:69]2)[CH:64]=[CH:63][C:60]=1[C:61]#[N:62]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 585760704-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium saltHCID 66672119HCID 66672119, compound

Product 1

HCID 58576912HCID 58576912, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-[4-(4-Trifluoromethyl-phenyl)-piperazin-1-yl]-butyric acid lithium salt (16 mg; 0.05 mmol, prepared in accordance with Example 3), diisopropylethyl amine (25 μL; 0.15 mmol) and tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (19 mg; 0.05 mmol) are diluted in a 2 to 1 mixture of dimethylformamide and tetrahydrofuran (1.5 mL) and the resulting solution is stirred for 5 minutes. A solution of 2-chloro-4-(piperidin-4-ylamino)-benzonitrile hydrochloride (14 mg; 0.05 mmol, prepared in accordance with Example 104) in dimethylformamide (0.5 mL) is added and the reaction is then stirred for 2 hours at room temperature. Following dilution with dichloromethane (10 mL), the organic layer is sequentially washed with water (5 mL), aq. sat. sodium hydrogen carbonate (3×5 mL), is dried over magnesium sulfate and concentrated under reduced pressure. The residue obtained is finally purified by preparative HPLC to deliver the desired product in pure form (12 mg; 0.02 mmol). The structure was confirmed using Protocol I-B. Calculated mass=534; observed mass=534; HPLC retention time=4.52 min.

Workup

  1. stirringthe reaction is then stirred for 2 hours at room temperature
  2. washthe organic layer is sequentially washed with water (5 mL), aq. sat. sodium hydrogen carbonate (3×5 mL)
  3. dry with materialis dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue obtained
  6. customis finally purified by preparative HPLC

Sources & evidence

ORD record
ord-badbf72011fb462fad9d7b2df5f7be48
Source dataset
uspto-grants-2015_08
Patent number
US09096524B2

Reaction notes

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