Sodium Bicarbonate → (E)-N-(4-amino-5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizin-8-yl)-4-(dimethylamino)-2-butenamide

HRID 336146Notes

Reaction equation

HRID 336146 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[N:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[C:27]([C:35]2[C:36]3[C:48]([NH2:49])=[N:47][CH:46]=[N:45][C:37]=3[N:38]3[C:43]=2[CH2:42][CH2:41][CH:40]([NH2:44])[CH2:39]3)[CH:26]=1.Cl.[CH3:51][N:52]([CH3:59])[CH2:53]/[CH:54]=[CH:55]/[C:56](O)=[O:57].C(=O)(O)[O-].[Na+]>CN(C=O)C>[NH2:49][C:48]1[C:36]2[C:35]([C:27]3[CH:26]=[N:25][C:34]4[C:29]([CH:28]=3)=[CH:30][CH:31]=[CH:32][CH:33]=4)=[C:43]3[N:38]([C:37]=2[N:45]=[CH:46][N:47]=1)[CH2:39][CH:40]([NH:44][C:56](=[O:57])/[CH:55]=[CH:54]/[CH2:53][N:52]([CH3:59])[CH3:51])[CH2:41][CH2:42]3

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 45358758(2E)-4-(Dimethylamino)-2-butenoic acid hydrochlorideHCID 867112835-(Quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizine-4,8-diamine

Product 1

HCID 71721577(E)-N-(4-amino-5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizin-8-yl)-4-(dimethylamino)-2-butenamideYield 54.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (10.3 mg) and 5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizine-4,8-diamine (8.8 mg) obtained in Step 11 of Example 1 were added to a solution of trans-4-dimethylaminocrotonic acid hydrochloride (4.5 mg) in DMF (0.5 ml) at room temperature. After being stirred for 1 hour at the same temperature, the mixture was poured into a saturated aqueous sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was then distilled off under reduced pressure. The resulting residue was purified by preparative thin-layer chromatography (produced by Wako, NH2 silica-gel 60 F254 plate, developing solvent: chloroform/methanol) to obtain the title compound as a light-yellow solid (6.4 mg).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. distillationthe solvent was then distilled off under reduced pressure
  4. customThe resulting residue was purified by preparative thin-layer chromatography (produced by Wako, NH2 silica-gel 60 F254 plate, developing solvent: chloroform/methanol)

Sources & evidence

ORD record
ord-9d74c321996546108d8d7e0fe803c386
Source dataset
uspto-grants-2014_11
Patent number
US08889666B2

Reaction notes

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