Diisopropylethylamine → (E)-methyl 3-(4-(8-morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-a]pyrazin-5-yl)benzamido)propanoate

HRID 1772706Notes

Reaction equation

HRID 1772706 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]3[N:9]([CH:22]=[C:23](/[CH:25]=[CH:26]/[C:27]4[CH:36]=[CH:35][C:34]5[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=5)[N:28]=4)[N:24]=3)[C:10]([C:13]3[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][CH:14]=3)=[CH:11][N:12]=2)[CH2:3][CH2:2]1.F[C:38](F)(F)[C:39]([OH:41])=[O:40].O1CC[N:47](C2C3N(C=C(/C=C/C4C=CC5C(=CC=CC=5)N=4)N=3)C(C3C=CC(C(O)=O)=CC=3)=CN=2)[CH2:46]C1.[CH3:80]OC(=O)[C@H](C)N.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.C(Cl)Cl>[O:1]1[CH2:2][CH2:3][N:4]([C:7]2[C:8]3[N:9]([CH:22]=[C:23](/[CH:25]=[CH:26]/[C:27]4[CH:36]=[CH:35][C:34]5[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=5)[N:28]=4)[N:24]=3)[C:10]([C:13]3[CH:14]=[CH:15][C:16]([C:17]([NH:47][CH2:46][CH2:38][C:39]([O:41][CH3:80])=[O:40])=[O:18])=[CH:20][CH:21]=3)=[CH:11][N:12]=2)[CH2:5][CH2:6]1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 82335L-Alanine methyl esterHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86345860(E)-4-(8-morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-a]pyrazin-5-yl)benzoic acidHCID 117728004(E)-4-(8-Morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-a]pyrazin-5-yl)benzoic acid trifluoroacetic acid salt

Product 1

HCID 117728293(E)-methyl 3-(4-(8-morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-a]pyrazin-5-yl)benzamido)propanoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

The (E)-4-(8-morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-a]pyrazin-5-yl)benzoic acid compound 57a (100.0 mg, 0.170 mmol) was treated with β alanine methyl ester (59.1 mg, 0.420 mmol), HATU (96.4 mg, 0.250 mmol), DIEA (0.175 mL, 1.00 mmol) in DMF (2 mL), and the mixture was stirred at rt for 3 h. The reaction was diluted with DCM and washed with water. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was triturated with MeOH, filtered and dried to give (E)-methyl 3-(4-(8-morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-a]pyrazin-5-yl)benzamido)propanoate which was subjected to saponification with LiOH, using the methods described in Example 15, Step C, to afford the title compound 39. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 2.54-2.57 (m, 1H), 3.46-3.57 (m, 3H), 3.77-3.88 (m, 4H), 4.26-4.36 (m, 4H), 7.46-7.51 (m, 1H), 7.56 (t, J=7.5 Hz, 1H), 7.65 (d, J=16.1 Hz, 1H), 7.70-7.91 (m, 5H), 7.96 (t, J=9.3 Hz, 2H), 8.00-8.11 (m, 2H), 8.25-8.30 (m, 1H), 8.35 (d, J=8.6 Hz, 1H), 8.75 (s, 1H). Mass Spectrum LCMS, ESI (pos.) Calcd. for C31H28N6O4: 572.2 [M+H]. found 572.5.

Workup

  1. washwashed with water
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was triturated with MeOH
  6. filtrationfiltered
  7. customdried

Sources & evidence

ORD record
ord-f0b521b001a14bd4be90b69a56a84308
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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