Diisopropylethylamine → HCID 90388474, compound

HRID 874453Notes

Reaction equation

HRID 874453 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:19]3=[C:20]4[C:14](=[C:15]5[N:24]([CH3:25])[CH:23]=[CH:22][C:21]([C:26](O)=[O:27])=[C:16]5[CH:17]=[CH:18]3)[C:13](=[O:29])[NH:12][C:11]4=[CH:10][CH2:9]2)=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[F:39][C:40]1[CH:41]=[CH:42][C:43]([O:48][CH3:49])=[C:44]([CH2:46][NH2:47])[CH:45]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C(=O)C>[F:39][C:40]1[CH:41]=[CH:42][C:43]([O:48][CH3:49])=[C:44]([CH:45]=1)[CH2:46][NH:47][C:26]([C:21]1[CH:22]=[CH:23][N:24]([CH3:25])[C:15]2[C:16]=1[CH:17]=[CH:18][C:19]1[N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[CH2:9][CH:10]=[C:11]3[NH:12][C:13](=[O:29])[C:14]=2[C:20]=13)=[O:27]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 183488291-(5-Fluoro-2-methoxyphenyl)methanamineHCID 90388390HCID 90388390, compound

Product 1

HCID 90388474HCID 90388474, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A stock solution of Example 56d and N,N-diisopropylethylamine (0.15 M and 0.42 M in N,N-dimethylacetamide, respectively, 254 μL) and (5-fluoro-2-methoxyphenyl)-methanamine (0.4 M in N,N-dimethylacetamide, 115 μL), and 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (0.22 M in N,N-dimethylacetamide, 254 μL) 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 100° C., and passed through the reactor at 180 μL min−1 (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 0.0016 g (8%) of the title compound. 1H NMR (400 MHz, DMSO-d6/D2O) δ 8.39 (d, J=2.14 Hz, 1H), 7.88 (s, 1H), 7.79 (dd, J=8.24, 2.14 Hz, 1H), 7.37 (d, J=8.24 Hz, 1H), 7.05 (m, 4H), 6.87 (m, 2H), 6.56 (m, 2H), 4.49 (s, 2H), 4.07 (s, 3H), 4.61 (m, 2H), 3.85 (s, 3H). MS (APCI+) m/z 527.2 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-e3ffcdecffe346ef9e9190a1deb43409
Source dataset
uspto-grants-2015_03
Patent number
US08980879B2

Reaction notes

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