Dimethylformamide → HCID 86710179, compound

HRID 2284411Notes

Reaction equation

HRID 2284411 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[C:5]2[N:11]=[CH:10][C:9]([C:12]3[CH:23]=[CH:22][C:15]([C:16]([NH:18][CH:19]4[CH2:21][CH2:20]4)=[O:17])=[CH:14][CH:13]=3)=[CH:8][C:6]=2[N:7]=1.[C:30]([O:34][C:35]([NH:37][C:38]1[N:43]=[CH:42][C:41](B(O)O)=[CH:40][N:39]=1)=[O:36])([CH3:33])([CH3:32])[CH3:31].P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN(C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH:19]1([NH:18][C:16]([C:15]2[CH:22]=[CH:23][C:12]([C:9]3[CH:10]=[N:11][C:5]4[C:4]([N:24]5[CH2:29][CH2:28][O:27][CH2:26][CH2:25]5)=[N:3][C:2]([C:41]5[CH:42]=[N:43][C:38]([NH:37][C:35](=[O:36])[O:34][C:30]([CH3:32])([CH3:31])[CH3:33])=[N:39][CH:40]=5)=[N:7][C:6]=4[CH:8]=3)=[CH:13][CH:14]=2)=[O:17])[CH2:21][CH2:20]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 62657Potassium Phosphate, TribasicHCID 45489688{2-[(tert-Butoxycarbonyl)amino]pyrimidin-5-yl}boronic acidHCID 86710178HCID 86710178, compound

Product 1

HCID 86710179HCID 86710179, compoundYield 48.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

To a 50 mL sealed tube, 4-(2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-N-cyclo-propylbenzamide (0.15 g, 0.00036 mol), (2-((tert-butoxycarbonyl)amino)pyrimidin-5-yl)boronic acid (0.113 g, 0.00047), potassium phosphate (0.155 g, 0.00072 mol), DMF (10 mL) and water (2 mL) were added. The reaction mixture was degassed with N2 for 5-10 minutes. To the same reaction mixture, Pd(PPh3)4 (0.022 g, 0.000018 mol) was added and degassed with N2 for 5-10 minutes. The reaction mixture was stirred at 95° C. for 1 hour. The reaction mass was cooled to room temperature and added ice cold water. A precipitate was obtained and the solid was collected by filtration. The solid was dissolved in chloroform, dried over anhydrous sodium sulfate and evaporated under reduced pressure to provide the crude product. The crude product was purified by flash column chromatography (2% methanol in chloroform) to provide the title compound (0.1 g, 48%). 1H NMR (300 MHz, DMSO-d6): δ 10.41 (br s, 1H), 9.47 (s, 1H), 9.19 (d, J=1.8 Hz, 1H), 6.59 (d, J=4.2 Hz, 1H), 8.51 (d, J=1.8 Hz, 1H), 7.98-8.08 (m, 4H), 4.57 (br s, 4H), 3.83 (s, 4H), 2.88-2.89 (m, 1H), 1.48 (s, 9H), 0.73 (d, J=5.4 Hz, 2H), 0.61 (d, J=3.0 Hz, 2H): LC-MS (ESI): Calculated mass: 568.2; Observed mass [M+H]+: 569.2. (RT=1.57 min).

Workup

  1. customTo a 50 mL sealed tube
  2. customThe reaction mixture was degassed with N2 for 5-10 minutes
  3. customdegassed with N2 for 5-10 minutes
  4. temperatureThe reaction mass was cooled to room temperature
  5. additionadded ice cold water
  6. customA precipitate was obtained
  7. filtrationthe solid was collected by filtration
  8. dissolutionThe solid was dissolved in chloroform
  9. dry with materialdried over anhydrous sodium sulfate
  10. customevaporated under reduced pressure
  11. customto provide the crude product
  12. customThe crude product was purified by flash column chromatography (2% methanol in chloroform)

Sources & evidence

ORD record
ord-fb2a71beb67e4b71ad114c51f964f5c5
Source dataset
uspto-grants-2015_09
Patent number
US09145411B2

Reaction notes

Loading…