Dimethylformamide → N-(4-(2-(5-(1,3-Dioxolan-2-yl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N-phenylcyclopropane-1,1-dicarboxamide

HRID 84383Notes

Reaction equation

HRID 84383 reaction equation
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:7]=[CH:8][C:9]([C:12]2[S:20][C:19]3[C:14](=[N:15][CH:16]=[CH:17][C:18]=3[O:21][C:22]3[CH:28]=[CH:27][C:25]([NH2:26])=[CH:24][C:23]=3[F:29])[CH:13]=2)=[N:10][CH:11]=1.CCN([CH:36]([CH3:38])[CH3:37])C(C)C.CN(C(ON1N=N[C:49]2[CH:50]=[CH:51][CH:52]=N[C:48]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:63]O.[C:65](OCC)(=[O:67])C.C[N:72]([CH:74]=[O:75])C>>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:7]=[CH:8][C:9]([C:12]2[S:20][C:19]3[C:14](=[N:15][CH:16]=[CH:17][C:18]=3[O:21][C:22]3[CH:28]=[CH:27][C:25]([N:26]([C:48]4[CH:49]=[CH:50][CH:51]=[CH:52][CH:63]=4)[C:65]([C:36]4([C:74]([NH2:72])=[O:75])[CH2:37][CH2:38]4)=[O:67])=[CH:24][C:23]=3[F:29])[CH:13]=2)=[N:10][CH:11]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21584119Ethylacetate methanolHCID 579195224-((2-(5-(1,3-Dioxolan-2-yl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yl)oxy)-3-fluoroaniline

Product 1

HCID 66599014N-(4-(2-(5-(1,3-Dioxolan-2-yl)pyridin-2-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N-phenylcyclopropane-1,1-dicarboxamideYield 34%

Procedure

To aniline 139 (Scheme 7) (0.46 g, 1.1 mmol) in dry DMF (20 mL) was added acid 1-(phenylcarbamoyl)cyclopropanecarbpxylic acid (0.46 g, 2.2 mmol), DIPEA (0.98 mL, 5.6 mmol) and HATU (1.07 g, 2.81 mmol) and the mixture was stirred at r.t. for 18 h. It was then partitioned between ethyl acetate and water; the organic phase was collected, washed with water, 1M NaOH, saturated NH4Cl, and brine, dried (MgSO4), filtered and concentrated. Silica gel chromatography of the residue (eluent 2% methanol/ethyl acetate) afforded 140 (0.23 g, 34% yield). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.37 (s, 1H), 9.98 (s, 1H), 8.68 (s, 1H), 8.53 (d, J=5.3 Hz, 1H), 8.40 (s, 1H), 8.31 (d, J=8.2 Hz, 1H), 7.97 (dd, J=8.2, 2.0 Hz, 1H), 7.90 (dd, J=13.1, 2.0 Hz, 1H), 7.62 (d, J=7.6, 2H), 7.53-7.46 (m, 2H), 7.30 (t, J=7.4 Hz, 2H), 7.06 (t, J=7.4 Hz, 1H), 6.66 (d, J=5.3 Hz, 1H), 5.88 (s, 1H), 4.11-3.97 (m, 4H), 1.47 (br s, 4H). MS (m/z): 597.2 (M+H).

Workup

  1. customIt was then partitioned between ethyl acetate and water
  2. customthe organic phase was collected
  3. washwashed with water, 1M NaOH, saturated NH4Cl, and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-251ad675361d46bdb76cb056766543cc
Source dataset
uspto-grants-2014_09
Patent number
US08846927B2

Reaction notes

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