Dimethylamine → HCID 86663610, compound

HRID 1520749Notes

Reaction equation

HRID 1520749 reaction equation
C1CC[CH:4]([N:7]=[C:8]=NC2CCCCC2)CC1.Br[CH2:17]/[CH:18]=[CH:19]/[C:20]([OH:22])=O.[C:23]([C:25]1[CH:26]=[C:27]([NH:31][C:32]2[C:33]3[CH:41]=[C:40]([NH2:42])[N:39]=[CH:38][C:34]=3[N:35]=[CH:36][N:37]=2)[CH:28]=[CH:29][CH:30]=1)#[CH:24].C(N(C(C)C)CC)(C)C.CNC.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.CC(N(C)C)=O>[CH3:4][N:7]([CH3:8])[CH2:17]/[CH:18]=[CH:19]/[C:20]([NH:42][C:40]1[N:39]=[CH:38][C:34]2[N:35]=[CH:36][N:37]=[C:32]([NH:31][C:27]3[CH:28]=[CH:29][CH:30]=[C:25]([C:23]#[CH:24])[CH:26]=3)[C:33]=2[CH:41]=1)=[O:22]

Participants

9

Reactant 6

HCID 674DimethylamineHCID 10340Sodium CarbonateHCID 10868DicyclohexylcarbodiimideHCID 81531DiisopropylethylamineHCID 64364114-Bromocrotonic acidHCID 86663609HCID 86663609, compound

Product 1

HCID 86663610HCID 86663610, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of DCC (7.23 g, 35.1 mmol) in dry THF (25 ml) at 0° C. under nitrogen, was added solid acid 9 (5.79 g, 35.1 mmol). The reaction mixture was stirred at 0° C. for 35 min before solid aniline 169 (1.83 g, 7.01 mmol) was added, followed by dry DMA (20 mL) and di-iso-propylethylamine (DIPEA) (6.11 ml, 35.1 mmol). The final reaction mixture was stirred at 0° C. for 45 min before being cooled to −15 to −20° C. (bath). 40% Aqueous dimethylamine (10.6 mL, 84.0 mmol) was then added and after 25 min the reaction mixture was poured into cold 2% aqueous sodium carbonate (200 mL) and the product was extracted into ethyl acetate (600 mL), which was washed successively with water (300 mL), cold 2% aqueous sodium carbonate (300 mL) and water (300 mL). The ethyl acetate solution was dried (Na2SO4) and evaporated under reduced pressure to give a solid which was purified by column chromatography on silica gel eluting with DCM/MeOH (gradient from 100:0 to 15:1), to give (2E)-4-(dimethylamino)-N-[4-(3-ethynylanilino)pyrido[3,4-d]pyrimidin-6-yl]-2-butenamide (171) (1.33 g, 51%) as a yellow/orange solid, mp 163-166° C. 1H NMR δ [(CD3)2SO] 10.89 (s, 1H), 10.25 (s, 1H), 9.02 (s, 1H), 9.00 (s, 1H), 8.63 (s, 1H), 8.02 (br s, 1H), 7.94-7.87 (m, 1H), 7.42 (t, J=7.9 Hz, 1H), 7.26 (br d, J=7.7 Hz, 1H), 6.88 (dt, J=15.4, 6.0 Hz, 1H), 6.52 (br d; J=15.4 Hz, 1H), 4.19 (s, 1H), 3.09 (dd, J=6.0, 1.2 Hz, 2H), 2.19 (s, 6H). Anal. Calcd for C21H20N6O.0.2H2O: C, 67.08; H, 5.47; N, 22.35%. Found C, 66.88; H, 5.47; N, 22.22%.

Workup

  1. additionwas added
  2. customThe final reaction mixture
  3. temperaturebefore being cooled to −15 to −20° C. (bath)
  4. extractionthe product was extracted into ethyl acetate (600 mL), which
  5. washwas washed successively with water (300 mL), cold 2% aqueous sodium carbonate (300 mL) and water (300 mL)
  6. dry with materialThe ethyl acetate solution was dried (Na2SO4)
  7. customevaporated under reduced pressure
  8. customto give a solid which
  9. customwas purified by column chromatography on silica gel eluting with DCM/MeOH (gradient from 100:0 to 15:1)

Sources & evidence

ORD record
ord-8657c85a67e341d9b13187a6a2568ef3
Source dataset
uspto-grants-2015_07
Patent number
US09073916B2

Reaction notes

Loading…