Diisopropylethylamine → HCID 178480475, compound

HRID 874452Notes

Reaction equation

HRID 874452 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.[Br:37][C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][C:39]=1[CH2:45][C:46](O)=[O:47].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C(=O)C>[Br:37][C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][C:39]=1[CH2:45][C:46]([NH: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:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=3)[CH2:18][CH:17]=[C:12]3[NH:13][C:14](=[O:16])[C:15]=2[C:11]=13)=[O:47]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27739272-(2-Bromo-5-fluorophenyl)acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178480427HCID 178480427, compound

Product 1

HCID 178480475HCID 178480475, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A stock solution of Example 23e and N,N-diisopropylethylamine (0.14 M and 0.40 M in N,N-dimethylacetamide, respectively, 287 μL) and 2-(2-bromo-5-fluorophenyl)acetic acid (0.4 M in N,N-dimethylacetamide, 124 μL), and 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (0.21 M in N,N-dimethylacetamide, 287 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 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 0.0058 g (24%) of the title compound. 1H NMR (400 MHz, DMSO-d6/D2O) δ 8.14 (d, J=2.44 Hz, 1H), 7.68 (dd, J=8.85, 5.49 Hz, 1H), 7.65 (s, 1H), 7.42 (dd, J=8.54, 2.44 Hz, 1H), 7.36 (dd, J=9.61, 3.20 Hz, 1H), 7.21 (d, J=8.54 Hz, 1H), 7.14 (td, J=8.54, 3.36 Hz, 1H), 7.04 (s, 1H), 6.82 (m, 2H), 6.49 (m, 2H), 5.02 (d, J=15.87 Hz, 1H), 4.18 (d, J=16.78 Hz, 1H), 4.03 (s, 3H), 3.92 (s, 2H). MS (APCI+) m/z 575.1 (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 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-3decd91c67d24a82a8bc122e29088989
Source dataset
uspto-grants-2015_03
Patent number
US08980879B2

Reaction notes

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