Dimethylamine → HCID 66823658, compound

HRID 1520739Notes

Reaction equation

HRID 1520739 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=O.[Br:7][C:8]1[CH:9]=[C:10]([NH:15][C:16]2[C:17]3[CH:25]=[C:24]([NH2:26])[N:23]=[CH:22][C:18]=3[N:19]=[CH:20][N:21]=2)[CH:11]=[CH:12][C:13]=1[F:14].[CH2:27]([N:29]([CH2:32]C)[CH2:30]C)[CH3:28].BrC/C=C/C(O)=O.N(C)C.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.C1COCC1.CC(N(C)C)=O>[Br:7][C:8]1[CH:9]=[C:10]([CH:11]=[CH:12][C:13]=1[F:14])[NH:15][C:16]1[C:17]2[CH:25]=[C:24]([NH:26][C:1](=[O:5])/[CH:2]=[CH:28]/[CH2:27][N:29]([CH3:32])[CH3:30])[N:23]=[CH:22][C:18]=2[N:19]=[CH:20][N:21]=1

Participants

10

Reactant 6

HCID 674DimethylamineHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 65578Oxalyl chloride2×HCID 64364114-Bromocrotonic acidHCID 10640427HCID 10640427, compound

Product 1

HCID 66823658HCID 66823658, compoundYield 45%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

Oxalyl chloride (508 mg, 4.00 mmol) was added to a solution of acid 159 (496 mg, 3.00 mmol) in dry dichloromethane (6 mL) and the mixture was stirred at room temperature for 40 min. The solution was then evaporated under reduced pressure at room temperature to give an oil which was dissolved in dry THF (5 mL) and added to a stirred mixture of compound 8a (668 mg, 2.00 mmol), triethylamine (0.84 mL, 6.00 mmol), and ITT (15 mL) at 0° C. After 1 h another batch of acid chloride preformed from oxalyl chloride (508 mg, 4.00 mmol) and acid 9 (496 mg, 3.00 mmol) was added and stirred further at 0° C. for another 30 min. A mixture of 40% NHMe2 (15.2 mL, 12.0 mmol) and DMA (10 mL) was added and the reaction mixture was stirred at 0° C. to room temperature for 19 h. Volatiles were evaporated under reduced pressure at 25° C. to give a brown oil which was stirred with 1% sodium carbonate solution (100 mL) at 0° C. for 30 min. The solid thus formed was collected by filtration, washed with water several times, and dried. Column chromatography of this material on silica gel eluting with dichloromethane to dichloromethane/MeOH (15:1) gave (2E)-N-[4-(3-bromo-4-fluoroanilino)pyrido[3,4-d]pyrimidin-6-yl]-4-(dimethylamino)-2-butenamide (161) (400 mg, 45%) as a yellow/orange solid, mp 163-166° C.; 1H NMR δ [(CD3)2SO] 10.96 (s, 1H), 10.33 (s, 1H), 9.02 (br s, 1H), 8.99 (br s, 1H), 8.63 (s, 1H), 8.24 (dd, J=6.4, 2.6 Hz, 1H), 7.92-7.84 (m, 1H), 7.44 (t, J=8.8 Hz, 1H), 6.87 (dt, J=15.5, 6.0 Hz, 1H), 6.52 (br d, J=15.5 Hz, 1H), 3.09 (dd, J=6.0, 1.2 Hz, 2H), 2.19 (s, 6H). Anal. Calcd for C19H18BrFN6O.MeOH: C, 50.33; H, 4.65; N, 17.61%. Found C, 50.38; H, 4.31; N, 17.86%.

Workup

  1. customThe solution was then evaporated under reduced pressure at room temperature
  2. customto give an oil which
  3. additionwas added
  4. stirringstirred further at 0° C. for another 30 min
  5. additionwas added
  6. stirringthe reaction mixture was stirred at 0° C. to room temperature for 19 h
  7. customVolatiles were evaporated under reduced pressure at 25° C.
  8. customto give a brown oil which
  9. customThe solid thus formed
  10. filtrationwas collected by filtration
  11. washwashed with water several times
  12. customdried

Sources & evidence

ORD record
ord-11f4e07e3aa34b8eb4b527f1a5fa1e1b
Source dataset
uspto-grants-2015_07
Patent number
US09073916B2

Reaction notes

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