Tetrahydrofuran → HCID 86601377, compound

HRID 852925Notes

Reaction equation

HRID 852925 reaction equation
CCN(CC)CC.[C:8]([O:12][C:13](=[O:42])[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[NH:21][C:22](=[O:41])[C:23]1[CH:28]=[CH:27][C:26]([CH2:29][NH:30][C:31]2[S:32][C:33]3[CH:39]=[C:38]([OH:40])[CH:37]=[CH:36][C:34]=3[N:35]=2)=[CH:25][CH:24]=1)([CH3:11])([CH3:10])[CH3:9].[NH2:43][CH2:44][CH2:45][N:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1.C1C[O:55][CH2:54]C1>>[C:8]([O:12][C:13](=[O:42])[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[NH:21][C:22](=[O:41])[C:23]1[CH:24]=[CH:25][C:26]([CH2:29][NH:30][C:31]2[S:32][C:33]3[CH:39]=[C:38]([O:40][C:54](=[O:55])[NH:43][CH2:44][CH2:45][N:46]4[CH2:51][CH2:50][O:49][CH2:48][CH2:47]4)[CH:37]=[CH:36][C:34]=3[N:35]=2)=[CH:27][CH:28]=1)([CH3:11])([CH3:9])[CH3:10]

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 8471TriethylamineHCID 4082852-MorpholinoethylamineHCID 86601378HCID 86601378, compound

Product 1

HCID 86601377HCID 86601377, compoundYield 30%

Conditions

Temperature
0 °C

Procedure

To a solution of p-nitrophenylchloroformate (171 mg, 0.848 mmol) in THF (15 mL) cooled to −78° C. under N2 atmosphere was added Et3N (236 μL, 1.70 mmol). Then a suspension of the intermediate 129 (416 mg, 0.848 mmol) in THF (4.2 mL) was added via canula. The resulting yellow mixture was stirred at −78° C. for 1 h and at 0° C. for 1.5 h, heated at 40° C. for 16 h and cooled to r.t. Then, neat 4-(2-aminoethyl)morpholine (119 μL, 0.848 mmol) was added and the solution was stirred for 4 h, quenched by addition of MeOH. It was allowed to stir for 30 min. and concentrated. The resulting material was purified by flash chromatography using MeOH/DCM (3:97) affording the title compound 132 (165 mg, 30% yield). 1H NMR: (DMSO-d6) δ (ppm): 9.77 (s, 1H), 8.64 (bs, 1H), 8.56 (t, J=5.9 Hz, 1H), 7.90 (d, J=8.2 Hz, 2H), 7.60 (t, J=5.9 Hz, 1H), 7.50 (d, J=8.0 Hz, 2H), 7.50-7.48 (m, 2H), 7.45 (d, J=2.3 Hz, 1H), 7.30 (d, J=8.8 Hz, 1H), 7.17 (t, J=7.6 Hz, 1H), 7.12 (t, J=7.8 Hz, 1H), 6.90 (dd, J=8.2, 2.0 Hz, 1H), 4.67 (d, J=6.0 Hz, 2H), 3.56 (t, J=4.1 Hz, 4H), 3.31 (t, J=6.1 Hz, 2H), 3.16 (q, J=6.1 Hz, 2H), 2.39 (t, J=6.8 Hz, 4H), 1.42 (s, 9H). m/z: 647.7 (MH+).

Workup

  1. additionwas added via canula
  2. temperatureheated at 40° C. for 16 h
  3. temperaturecooled to r.t
  4. stirringthe solution was stirred for 4 h
  5. customquenched by addition of MeOH
  6. stirringto stir for 30 min.
  7. concentrationconcentrated
  8. customThe resulting material was purified by flash chromatography

Sources & evidence

ORD record
ord-205dc592f7e949e6bb528cb0ac593ea8
Source dataset
uspto-grants-2007_08
Patent number
US07253204B2

Reaction notes

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