Dimethylformamide → HCID 86710175, compound

HRID 2284407Notes

Reaction equation

HRID 2284407 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[N:11]=[CH:10][C:9]([C:12]3[CH:13]=[C:14]([NH:18][C:19](=[O:21])[CH3:20])[CH:15]=[CH:16][CH:17]=3)=[CH:8][C:6]=2[N:7]=1.[C:28]([O:32][C:33]([NH:35][C:36]1[N:41]=[CH:40][C:39](B(O)O)=[CH:38][N:37]=1)=[O:34])([CH3:31])([CH3:30])[CH3:29].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>[C:19]([NH:18][C:14]1[CH:13]=[C:12]([C:9]2[CH:10]=[N:11][C:5]3[C:4]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)=[N:3][C:2]([C:39]4[CH:40]=[N:41][C:36]([NH:35][C:33](=[O:34])[O:32][C:28]([CH3:30])([CH3:29])[CH3:31])=[N:37][CH:38]=4)=[N:7][C:6]=3[CH:8]=2)[CH:17]=[CH:16][CH:15]=1)(=[O:21])[CH3:20]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 62657Potassium Phosphate, TribasicHCID 45489688{2-[(tert-Butoxycarbonyl)amino]pyrimidin-5-yl}boronic acidHCID 86710174HCID 86710174, compound

Product 1

HCID 86710175HCID 86710175, compoundYield 89.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
105 °C

Procedure

To a 50 mL sealed tube, N-(3-(2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-7-yl)-phenyl)acetamide (1.30 g, 0.0033 mol), (2-((tert-butoxycarbonyl)amino)pyrimidin-5-yl)boronic acid (1.21 g, 0.0050 mol), potassium phosphate (K3PO4) (1.43 g, 0.0067 mol), DMF (35 mL) and water (9 mL) were added. The reaction mixture was degassed with N2 for 5-10 minutes. To the same reaction mixture, Pd(PPh3)4 (0.274 g, 0.00023 mol) was added and again degassed with N2 for 5-10 minutes. The reaction mixture was stirred at 105° C. for 2 hours. The reaction mass was cooled and added to ice cold water. The precipitate was obtained and 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 column chromatography (60-120 silica gel, 3% methanol in chloroform) to provide the title compound (1.6 g, 87.4%). NMR (300 MHz, DMSO-d6): δ 10.42 (s, 1H), 10.15 (s, 1H), 9.47 (s, 1H), 9.05 (d, J=2.4 Hz, 1H), 8.29 (d, J=2.1 Hz, 1H), 8.17 (s, 1H), 7.63 (t, J=8.4 Hz, 2H), 7.49 (t, J=7.8 Hz, 1H), 4.56 (br s, 4H), 3.85 (t, J=3.9 Hz, 4H), 2.10 (s, 3H), 1.49 (s, 9H): LC-MS (ESI): Calculated mass: 542.2; Observed mass [M+H]+: 542.9. (RT=1.39 min).

Workup

  1. customTo a 50 mL sealed tube
  2. customThe reaction mixture was degassed with N2 for 5-10 minutes
  3. customagain degassed with N2 for 5-10 minutes
  4. temperatureThe reaction mass was cooled
  5. additionadded to ice cold water
  6. customThe precipitate was obtained
  7. filtrationwas 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 column chromatography (60-120 silica gel, 3% methanol in chloroform)

Sources & evidence

ORD record
ord-60ed68a59c38494b9f3e2417de58aa6b
Source dataset
uspto-grants-2015_09
Patent number
US09145411B2

Reaction notes

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