Diisopropylethylamine → HCID 59619453, compound

HRID 1367514Notes

Reaction equation

HRID 1367514 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C@@H:11]2[CH2:15][C@@H:14]([C:16](O)=[O:17])[C@H:13]([C:19]([N:21]3[CH2:24][C:23]([F:26])([F:25])[CH2:22]3)=[O:20])[CH2:12]2)(=[O:10])=[O:9])=[C:4]([C:27]([F:30])([F:29])[F:28])[CH:3]=1.C(N(CC)C(C)C)(C)C.C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)[C:53]2[N:54]=C[CH:56]=[CH:57][C:52]=2[N:51]=N1.F[P-](F)(F)(F)(F)F.C1C(N)(C#N)C1.Cl>C(#N)C>[C:53]([C:52]1([NH:51][C:16]([C@@H:14]2[CH2:15][C@@H:11]([S:8]([C:5]3[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=3[C:27]([F:29])([F:30])[F:28])(=[O:10])=[O:9])[CH2:12][C@H:13]2[C:19]([N:21]2[CH2:22][C:23]([F:25])([F:26])[CH2:24]2)=[O:20])=[O:17])[CH2:56][CH2:57]1)#[N:54]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 145863631-Amino-1-cyclopropanecarbonitrile hydrochlorideHCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate MethanaminiumHCID 86649026HCID 86649026, compound

Product 1

HCID 59619453HCID 59619453, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of (1R,2R,4S)-4-(4-Bromo-2-trifluoromethyl-benzenesulfonyl)-2-(3,3-difluoro-azetidine-1-carbonyl)-cyclopentanecarboxylic acid (150 mg, 0.29 mmol), N,N-diisopropylethylamine (0.15 mL, 0.87 mmol), 2-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (221 mg, 0.58 mmol) in acetonitrile was added 1-amino-cyclopropyl cyanic hydrochloride (41 mg, 0.34 mmol). The reaction mixture was stirred at room temperature for 16 h then concentrated in vacuo and partitioned between ethyl acetate and an aqueous solution of sodium carbonate (5% w/w). The aqueous layer was extracted with ethyl acetate then the combined organic layers were washed with aqueous hydrochloric acid (1N) and brine then dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with a gradient of dichloromethane/methanol (98:2 v/v) as eluant to afford the title compound (144 mg, 85%) as a brown solid. MS (EI): 584.0 (M−H)−.

Workup

  1. concentrationthen concentrated in vacuo
  2. custompartitioned between ethyl acetate
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. washthe combined organic layers were washed with aqueous hydrochloric acid (1N) and brine
  5. dry with materialthen dried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel with a gradient of dichloromethane/methanol (98:2 v/v) as eluant

Sources & evidence

ORD record
ord-709e4a2601904c6bb3ed54a1625e74b0
Source dataset
uspto-grants-2011_02
Patent number
US07893099B2

Reaction notes

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