Ammonia → HCID 178484948, compound

HRID 1192862Notes

Reaction equation

HRID 1192862 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:16](=[O:17])[C:12]3([CH2:15][CH2:14][CH2:13]3)[N:11]([C:18]3[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][CH2:26][C:27]([NH:29][CH3:30])=O)=[CH:20][CH:19]=3)[C:10]2=[S:31])=[CH:5][C:4]=1[C:32]([F:35])([F:34])[F:33])#[N:2].[N:36]1C=CC=CC=1.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.N>ClCCl>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:16](=[O:17])[C:12]3([CH2:15][CH2:14][CH2:13]3)[N:11]([C:18]3[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][CH2:26][C:27](=[NH:36])[NH:29][CH3:30])=[CH:20][CH:19]=3)[C:10]2=[S:31])=[CH:5][C:4]=1[C:32]([F:34])([F:35])[F:33])#[N:2]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 15951524HCID 15951524, compound

Product 1

HCID 178484948HCID 178484948, compoundYield 72.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-{4-[7-(4-Cyano-3-trifluoromethylphenyl)-8-oxo-6-thioxo-5,7-diaza-spiro[3.4]oct-5-yl]-phenyl}-N-methyl-butyramide (88) [ND-6] (4.0 mg, 0.008 mmol) and pyridine (1.94 μL, 0.02 mmol) in dichloromethane (3 mL) at −40° C. was slowly added triflic anhydride (Tf2O, 1.75 μL, 0.01 mmol). The mixture was allowed to warm to 0° C. over 3 h. The solution was then cooled to −40° C. and ammonia was introduced by bubbling. The reaction was then warmed to room temperature and stirred overnight. Without aqueous work up, flash chromatography using 10% methanol in ethyl acetate afforded 4-(4-(7-(4-Cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-an-5-yl)phenyl)-N-methylbutanimidamide (87) [ND-3] (2.9 mg, 72%) of as a colorless oil: 1H NMR (CD3CN) δ 8.10 (d, 1H, J=8.2 Hz) 8.04 (s, 1H), 7.92 (d, 1H, J=8.2 Hz) 7.49 (br s, 2H), 7.43 (d, 2H, J=8.3 Hz), 7.30 (d, 2H, J=8.3 Hz) 3.26 (d, 3H, J=5.4 Hz) 2.77 (t, 2H, J=8.0 Hz) 2.56-2.65 (m, 2H), 2.52 (t, 2H, J=7.7 Hz) 2.42-2.52 (m, 2H), 1.95-2.12 (m, 3H), 1.47-1.62 (m, 1H).

Workup

  1. customat −40° C.
  2. temperatureThe solution was then cooled to −40° C.
  3. customby bubbling
  4. temperatureThe reaction was then warmed to room temperature

Sources & evidence

ORD record
ord-11ab951871104067bfdcbc161a3d7c17
Source dataset
uspto-grants-2014_03
Patent number
US08680291B2

Reaction notes

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