Diisopropylethylamine → HCID 178480474, compound

HRID 874442Notes

Reaction equation

HRID 874442 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][N:5]([CH3:27])[C:6]2[C:7]=1[CH:8]=[N: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.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:61][C:62]1[CH:67]=[CH:66][C:65]([CH2:68][C:69](O)=[O:70])=[C:64]([F:72])[CH:63]=1>CN(C)C(=O)C>[Cl:61][C:62]1[CH:67]=[CH:66][C:65]([CH2:68][C:69]([NH:1][C:2]2[CH:3]=[CH:4][N:5]([CH3:27])[C:6]3[C:7]=2[CH:8]=[N:9][C:10]2[N:19]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[CH2:18][CH:17]=[C:12]4[NH:13][C:14](=[O:16])[C:15]=3[C:11]=24)=[O:70])=[C:64]([F:72])[CH:63]=1

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 2757563(4-Chloro-2-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 178480438HCID 178480438, compound

Product 1

HCID 178480474HCID 178480474, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A stock solution of Example 14e and N,N-diisopropylethylamine (0.11 M and 0.33 M in N,N-dimethylacetamide, respectively, 350 μL, 0.038 mmol Example 14e and 0.11 mmol N,N-diisopropylethylamine), 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (0.13 M in N,N-dimethylacetamide, 350 μL, 0.046 mmol), and 2-(4-chloro-2-fluorophenyl)acetic acid (0.40 M in N,N-dimethylacetamide, 113 μL, 0.050 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 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 yield the title compound as an impure mixture. The material was dissolved in methanol (1 mL) and manually injected into the HPLC(C8, acetonitrile/water (0.1% ammonium acetate), 5-100%) to give 0.0036 g (19%) of the title compound. 1H NMR (400 MHz, DMSO-d6/D2O) δ 8.52 (d, J=2.75 Hz, 1H), 8.43 (d, J=2.75 Hz, 1H), 7.76 (s, 1H), 7.47 (t, J=8.24 Hz, 1H), 7.42 (dd, J=9.77, 1.83 Hz, 1H), 7.30 (dd, J=8.09, 1.68 Hz, 1H), 7.07 (s, 1H), 6.87 (m, 2H), 6.58 (m, 2H), 4.61 (s, 2H), 4.05 (s, 3H), 3.82 (s, 2H). MS (APCI+) m/z 532.0 (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-5dbe44a17edc442e919677a7ed06407c
Source dataset
uspto-grants-2015_03
Patent number
US08980879B2

Reaction notes

Loading…