Diisopropylethylamine → HCID 178491801, compound

HRID 874454Notes

Reaction equation

HRID 874454 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.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:61][C:62]1[CH:63]=[CH:64][C:65]([O:72][CH3:73])=[C:66]([CH2:68][C:69](O)=[O:70])[CH:67]=1>CN(C)C(=O)C>[F:61][C:62]1[CH:63]=[CH:64][C:65]([O:72][CH3:73])=[C:66]([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]=[CH:9][C:10]2[N:19]([C:20]4[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=4)[CH2:18][CH:17]=[C:12]4[NH:13][C:14](=[O:16])[C:15]=3[C:11]=24)=[O:70])[CH:67]=1

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 3026845-Fluoro-2-methoxyphenylacetic 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 178491801HCID 178491801, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A stock solution of Example 23e and N,N-diisopropylethylamine (0.09 M and 0.25 M in N,N-dimethylacetamide, respectively, 450 μL, 0.2 mmol Example 23e and 0.6 mmol N,N-diisopropylethylamine), 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (0.14 M in N,N-dimethylacetamide, 450 μL, 0.3 mmol), and 2-(5-fluoro-2-methoxyphenyl)acetic acid (0.40 M in N,N-dimethylacetamide, 125 μL, 0.24 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 min−1 (10 minute residence time). Upon exiting the reactor, the reaction mixture was loaded directly into an injection loop and purified using reverse phase HPLC(C8, acetonitrile/water (0.1% TFA), 5-100%) to give 0.0243 g (91%) of the title compound as the TFA salt. 1H NMR (400 MHz, DMSO-d6/D2O) δ 10.28 (s, 1H), 8.12 (d, J=2.44 Hz, 1H), 7.65 (s, 1H), 7.42 (dd, J=8.54, 2.44 Hz, 1H), 7.20 (d, J=8.54 Hz, 1H), 7.11 (m, 2H), 7.04 (s, 1H), 7.01 (m, 1H), 6.83 (m, 2H), 6.48 (m, 2H), 5.02 (d, J=15.56 Hz, 1H), 4.18 (d, J=15.87 Hz, 1H), 4.04 (s, 3H), 3.79 (s, 3H), 3.70 (s, 2H). MS (APCI+) m/z 527.1 (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 min−1 (10 minute residence time)
  4. custompurified

Sources & evidence

ORD record
ord-f1e8f35b946746d2a0aa7c43008bc556
Source dataset
uspto-grants-2015_03
Patent number
US08980879B2

Reaction notes

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