Diisopropylethylamine → HCID 67443231, compound

HRID 1400823Notes

Reaction equation

HRID 1400823 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[N:21]=[CH:20][C:19]([CH2:22][N:23]5[CH2:27][CH2:26][CH2:25][C:24]5=[O:28])=[CH:18][CH:17]=4)[S:15][C:8]=23)=[C:4]([F:31])[CH:3]=1.CCN(C(C)C)C(C)C.Cl[C:42](OC1C=CC([N+]([O-])=O)=CC=1)=[O:43].Cl.[CH3:55][S:56]([C:59]1[CH:60]=[C:61]([CH:63]=[CH:64][CH:65]=1)[NH2:62])(=[O:58])=[O:57]>C1COCC1>[F:31][C:4]1[CH:3]=[C:2]([NH:1][C:42]([NH:62][C:61]2[CH:63]=[CH:64][CH:65]=[C:59]([S:56]([CH3:55])(=[O:57])=[O:58])[CH:60]=2)=[O:43])[CH:30]=[CH:29][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]3[CH:17]=[CH:18][C:19]([CH2:22][N:23]4[CH2:27][CH2:26][CH2:25][C:24]4=[O:28])=[CH:20][N:21]=3)[S:15][C:8]=12

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 27351793-(Methylsulfonyl)aniline hydrochlorideHCID 58474708HCID 58474708, compound

Product 1

HCID 67443231HCID 67443231, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 104 (50 mg, 0.115 mmol) in THF (2.3 mL) under nitrogen at −78° C. was added DIPEA (201 μl, 1.151 mmol) followed by 4-nitrophenyl chloroformate (116 mg, 0.575 mmol). The reaction mixture was kept at −78° C. over 1 hour. 3-(Methylsulfonyl)aniline hydrochloride (143 mg, 0.690 mmol) was added at −78° C. and the reaction mixture was allowed to warm to room temperature slowly. The reaction mixture was then quenched by addition of methanol, concentrated, dissolved in ethyl acetate, and successively washed with NH4Cl and NaHCO3, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by Biotage (SNAP 25 g cartridge; MeOH/DCM: 0/100 to 20/80 over 20 CV), to afford the title compound 105 (14.8 mg, 0.023 mmol, 20% yield) as beige solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 9.28 (s, 1H), 9.21 (s, 1H), 8.54 (d, J=5.6 Hz, 1H), 8.53 (d, J=2.4 Hz, 1H), 8.36 (s, 1H), 8.27 (d, J=8.4 Hz, 1H), 8.18 (t, J=2.0 Hz, 1H), 7.82-7.74 (m, 2H), 7.70 (dt, J=8.0, 1.6 Hz, 1H), 7.59 (t, J=8.0 Hz, 1H), 7.55 (dt, J=8.0, 1.6 Hz, 1H), 7.47 (t, J=8.8 Hz, 1H), 7.31 (d, J=8.8 Hz, 1H), 6.69 (d, J=5.2 Hz, 1H), 4.46 (s, 2H), 3.40-3.28 (m, 2H, hidden under water peak), 3.21 (s, 3H), 2.31 (t, J=8.0 Hz, 2H), 1.95 (quint, J=7.6 Hz, 2H). MS (m/z): 632.5 (M+H).

Workup

  1. customThe reaction mixture was then quenched by addition of methanol
  2. concentrationconcentrated
  3. dissolutiondissolved in ethyl acetate
  4. washsuccessively washed with NH4Cl and NaHCO3
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by Biotage (SNAP 25 g cartridge; MeOH/DCM: 0/100 to 20/80 over 20 CV)

Sources & evidence

ORD record
ord-12c24097b9a0440e92db621396cdd199
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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