Diisopropylethylamine → HCID 67441914, compound

HRID 1400894Notes

Reaction equation

HRID 1400894 reaction equation
Cl.Cl.[CH:3]1([NH:6][C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][N:20]=[C:19]4[CH:23]=[C:24]([C:26]5[CH2:27][CH2:28][NH:29][CH2:30][CH:31]=5)[S:25][C:18]=34)=[C:12]([F:32])[CH:11]=2)=[O:8])[CH2:5][CH2:4]1.CCN(C(C)C)C(C)C.Cl[CH2:43][CH2:44][CH2:45][N:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1>CN(C=O)C.O>[CH:3]1([NH:6][C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][N:20]=[C:19]4[CH:23]=[C:24]([C:26]5[CH2:27][CH2:28][N:29]([CH2:43][CH2:44][CH2:45][N:46]6[CH2:51][CH2:50][O:49][CH2:48][CH2:47]6)[CH2:30][CH:31]=5)[S:25][C:18]=34)=[C:12]([F:32])[CH:11]=2)=[O:8])[CH2:5][CH2:4]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 958344-(3-Chloropropyl)morpholine2×HCID 67442257HCID 67442257, compound

Product 1

HCID 67441914HCID 67441914, compoundYield 23.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of compound 271 (150 mg, 0.302 mmol) and DIPEA (227 μl, 1.302 mmol) in DMF (10 mL) was added 4-(3-chloropropyl)morpholine (53.3 mg, 0.325 mmol). The reaction mixture was stirred at 50° C. for 2 h. More 4-(3-chloropropyl)morpholine (212 mg, 1.3 mmol) was added in 4 h and the reaction mixture was heated at 50° C. for an additional 19 h. The reaction mixture was then diluted with water and extracted with EtOAc. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by Biotage (SNAP 80 g cartridge; MeOH/DCM: 0/100 to 15/85 over 20 CV) to produce a material that upon trituration with AcOEt afforded title compound 276 (40 mg, 0.07 mmol, 22% yield) as beige solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.77 (s, 1H), 8.44 (d, J=5.2 Hz, 1H), 7.71 (dd, J=2.4 and 13.6 Hz, 1H), 7.48 (s, 1H), 7.34 (t, J=9.2 Hz, 1H), 7.22-7.18 (m, 1H), 6.60 (d, J=2.4 Hz, 1H), 6.55 (d, J=5.2 Hz, 1H), 6.37 (s, 1H), 3.56 (q, J=4.8 Hz, 4H), 3.12 (bs, 2H), 2.70-2.62 (m, 2H), 2.62-2.58 (m, 2H), 2.58-2.50 (m, 1H), 2.43 (t, J=7.2 Hz, 2H), 2.40-2.32 (m, 2H), 2.30 (t, J=7.2 Hz, 2H), 1.64 (quint, J=6.8 Hz, 2H), 0.66-0.62 (m, 2H), 0.44-0.41 (m, 2H). MS (m/z): 552.4. (M+H).

Workup

  1. temperaturethe reaction mixture was heated at 50° C. for an additional 19 h
  2. extractionextracted with EtOAc
  3. extractionThe organic extract
  4. washwas washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by Biotage (SNAP 80 g cartridge; MeOH/DCM: 0/100 to 15/85 over 20 CV)
  9. customto produce a material that upon trituration with AcOEt

Sources & evidence

ORD record
ord-34ae681bde804c6fb19c7f28c94b1444
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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