Potassium Acetate → HCID 66600288, compound

HRID 1621642Notes

Reaction equation

HRID 1621642 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[CH:3]=1.[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][N:38]([CH2:41][C:42]2[CH:43]=[C:44](B(O)O)[C:45]([F:48])=[N:46][CH:47]=2)[CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29].C([O-])(=O)C.[K+]>C(O)C.O>[CH3:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][N:9]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[C:4]2[N:5]=[C:6]([CH3:8])[N:7]=[C:2]([C:44]3[CH:43]=[C:42]([CH2:41][N:38]4[CH2:39][CH2:40][N:35]([C:33]([O:32][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:34])[CH2:36][CH2:37]4)[CH:47]=[N:46][C:45]=3[F:48])[CH:3]=2)=[CH:12][CH:13]=1

Participants

6

Reactant 3

HCID 517044Potassium AcetateHCID 59548218(5-((4-(tert-Butoxycarbonyl)piperazin-1-yl)methyl)-2-fluoropyridin-3-yl)boronic acidHCID 595484046-chloro-N,N-bis(4-methoxybenzyl)-2-methylpyrimidin-4-amine

Product 1

HCID 66600288HCID 66600288, compoundYield 42.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

6-Chloro-N,N-bis(4-methoxybenzyl)-2-methylpyrimidin-4-amine (214.0 mg, 0.557 mmol), 5-((4-(tert-butoxycarbonyl)piperazin-1-yl)methyl)-2-fluoropyridin-3-ylboronic acid (Example 34, Step 3)(189 mg, 0.557 mmol), PdCl2 (AmPhos)2 (Aldrich, St. Louis, Mo.) (19.74 mg, 0.028 mmol), and potassium acetate (164 mg, 1.672 mmol) in a mixture of ethanol (3.0 mL) and water (0.300 mL) was sparged with argon and then heated (microwave) at 100° C. in a 20 mL microwave vial for 20 min. The reaction mixture was then concentrated onto silica gel and chromatographically purified (ISCO, 24 g, 0 to 100% EtOAc/Hexanes) to provide tert-butyl 4-((5-(6-(bis(4-methoxybenzyl)amino)-2-methylpyrimidin-4-yl)-6-fluoropyridin-3-yl)methyl)piperazine-1-carboxylate (152.0 mg, 0.236 mmol, 42.4% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.44 (dd, J=9.39, 2.15 Hz, 1H); 8.14 (s, 1H); 7.17 (d, J=7.82 Hz, 4H); 6.86 (d, J=8.61 Hz, 5H); 4.74 (br. s., 4H); 3.79 (s, 6H); 3.55 (s, 2H); 3.42 (t, J=4.69 Hz, 4H); 2.62 (s, 3H); 2.37-2.43 (m, 4H); 1.45 (s, 9H). 19F NMR (377 MHz, CDCl3) 6-71.01 (d, J=9.16 Hz, 1F). m/z (ESI, +ve ion) 643.2 (M+H)+.

Workup

  1. customwas sparged with argon
  2. concentrationThe reaction mixture was then concentrated onto silica gel
  3. customchromatographically purified (ISCO, 24 g, 0 to 100% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-16d11fbddce5408fa1628a3b8008a2a7
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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