Diisopropylethylamine → 1-(5-(4-fluorophenyl)-11-methyl-1-oxo-2,4,5,11-tetrahydro-1H-2,5,11-triazadibenzo[cd,h]azulen-8-yl)-3-(3-phenoxyphenyl)urea

HRID 874450Notes

Reaction equation

HRID 874450 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][N:5]([CH3:27])[C:6]2[C:7]=1[CH:8]=[CH:9][C:10]1[N:19]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[CH2:18][CH:17]=[C:12]3[NH:13][C:14](=[O:16])[C:15]=2[C:11]=13.C(N(CC)C(C)C)(C)C.[N:37]([C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([O:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH:41]=1)=[C:38]=[O:39]>CN(C)C(=O)C>[F:26][C:23]1[CH:22]=[CH:21][C:20]([N:19]2[C:10]3=[C:11]4[C:15](=[C:6]5[N:5]([CH3:27])[CH:4]=[CH:3][C:2]([NH:1][C:38]([NH:37][C:40]6[CH:45]=[CH:44][CH:43]=[C:42]([O:46][C:47]7[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=7)[CH:41]=6)=[O:39])=[C:7]5[CH:8]=[CH:9]3)[C:14](=[O:16])[NH:13][C:12]4=[CH:17][CH2:18]2)=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 34456731-Isocyanato-3-phenoxybenzeneHCID 178480427HCID 178480427, compound

Product 1

HCID 903877661-(5-(4-fluorophenyl)-11-methyl-1-oxo-2,4,5,11-tetrahydro-1H-2,5,11-triazadibenzo[cd,h]azulen-8-yl)-3-(3-phenoxyphenyl)ureaYield 28%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A stock solution of Example 23e and N,N-diisopropylethylamine (0.0875 M and 0.042 in N,N-dimethylacetamide, respectively, 497 μL, 0.042 mmol Example 23e and 0.126 mmol N,N-diisopropylethylamine) and 1-isocyanato-3-phenoxybenzene (0.40 M in N,N-dimethylacetamide, 208 μL, 0.084 mmol) were aspirated from their respective source vials, mixed through a perfluoroalkoxy mixing tube (0.2 mm inner diameter), and loaded into an injection loop. The reaction segment was injected into the flow reactor (Hastelloy coil, 0.75 mm inner diameter, 1.8 mL internal volume) set at 150° C., and passed through the reactor at 180 μL per minute (10 minute residence time). Upon exiting the reactor, the reaction mixture was loaded directly into an injection loop and purified by reverse phase HPLC(C8, acetonitrile/water (0.1% ammonium acetate), 5-100%) to give 0.0067 g (28%) of the title compound. 1H NMR (400 MHz, DMSO-d6/D2O) δ 7.90 (d, J=2.44 Hz, 1H), 7.60 (s, 1H), 7.40 (m, 2H), 7.27 (m, 3H), 7.16 (m, 3H), 7.03 (m, 2H), 6.97 (s, 1H), 6.78 (m, 2H), 6.64 (m, 1H), 6.51 (m, 2H), 4.60 (m, 2H), 4.06 (s, 3H). MS (APCI+) m/z 572.1 (M+H)+.

Workup

  1. additionmixed through a perfluoroalkoxy mixing tube (0.2 mm inner diameter)
  2. customset at 150° C.
  3. custompassed through the reactor at 180 μL per minute (10 minute residence time)
  4. custompurified by reverse phase HPLC(C8, acetonitrile/water (0.1% ammonium acetate), 5-100%)

Sources & evidence

ORD record
ord-b890c7abb4d14dedba37ab9203e977ee
Source dataset
uspto-grants-2015_03
Patent number
US08980879B2

Reaction notes

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