Diisopropylethylamine → (E)-Methyl 3-(4-(8-morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-b]pyridazin-3-yl)benzamido)propanoate

HRID 718574Notes

Reaction equation

HRID 718574 reaction equation
FC(F)(F)C(O)=O.[O:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:15]3[N:16]([C:20]([C:35]4[CH:43]=[CH:42][C:38]([C:39]([OH:41])=O)=[CH:37][CH:36]=4)=[C:21](/[CH:23]=[CH:24]/[C:25]4[CH:34]=[CH:33][C:32]5[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=5)[N:26]=4)[N:22]=3)[N:17]=[CH:18][CH:19]=2)[CH2:10][CH2:9]1.[NH2:44][CH2:45][CH2:46][C:47]([O:49][CH3:50])=[O:48].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[O:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:15]3[N:16]([C:20]([C:35]4[CH:36]=[CH:37][C:38]([C:39]([NH:44][CH2:45][CH2:46][C:47]([O:49][CH3:50])=[O:48])=[O:41])=[CH:42][CH:43]=4)=[C:21](/[CH:23]=[CH:24]/[C:25]4[CH:34]=[CH:33][C:32]5[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=5)[N:26]=4)[N:22]=3)[N:17]=[CH:18][CH:19]=2)[CH2:10][CH2:9]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 192794Methyl beta-alanateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117728839(E)-4-(8-Morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-b]pyridazin-3-yl)benzoic acid trifluoroacetic acid salt

Product 1

HCID 117732459(E)-Methyl 3-(4-(8-morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-b]pyridazin-3-yl)benzamido)propanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of Compound 40 (0.21 g, 0.36 mmol, Example 5) in DMF (3 mL) was added methyl 3-aminopropanoate (0.12 g, 0.89 mmol), HATU (0.20 g, 0.53 mmol) and DIEA (0.37 mL, 2.1 mmol). The resulting mixture was stirred at rt for 16 h and poured into water (20 mL). The aqueous layer was extracted with DCM (2×20 mL). The combined organic layers were dried over MgSO4 and filtered. Upon removal of the solvent, the resultant residue was purified by flash chromatography on silica gel (40-100% EtOAc/heptane) to give compound 7a as a red solid. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.12 (d, J=8.8 Hz, 1H), 8.07 (d, J=8.6 Hz, 1H), 7.92-8.03 (m, 4H), 7.84 (d, J=8.6 Hz, 2H), 7.78 (d, J=8.1 Hz, 1H), 7.65-7.76 (m, 3H), 7.46-7.54 (m, 1H), 6.97 (t, J=6.0 Hz, 1H), 6.13 (d, J=5.6 Hz, 1H), 4.06-4.13 (m, 4H), 3.96-4.03 (m, 4H), 3.76-3.83 (m, 2H), 3.75 (s, 3H), 2.71 (t, J=5.9 Hz, 2H).

Workup

  1. extractionThe aqueous layer was extracted with DCM (2×20 mL)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. customUpon removal of the solvent
  5. customthe resultant residue was purified by flash chromatography on silica gel (40-100% EtOAc/heptane)

Sources & evidence

ORD record
ord-aee660462e3840ec86f0fcc507f915e9
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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