Sodium Iodide → N-[6-(2-Acetylaminoethylamino)-2-phenylpyrimidin-4-yl]-2-[4-(2-chlorophenoxy)-piperidin-1-yl]-acetamide

HRID 895471Notes

Reaction equation

HRID 895471 reaction equation
[I-].[Na+].[C:3]([NH:6][CH2:7][CH2:8][NH:9][C:10]1[N:15]=[C:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:13]=[C:12]([NH:22][C:23](=[O:26])[CH2:24]Cl)[CH:11]=1)(=[O:5])[CH3:4].[Cl:27][C:28]1[CH:40]=[CH:39][CH:38]=[CH:37][C:29]=1[O:30][CH:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.CCN(C(C)C)C(C)C>C1COCC1.C(#N)C>[C:3]([NH:6][CH2:7][CH2:8][NH:9][C:10]1[N:15]=[C:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:13]=[C:12]([NH:22][C:23](=[O:26])[CH2:24][N:34]2[CH2:33][CH2:32][CH:31]([O:30][C:29]3[CH:37]=[CH:38][CH:39]=[CH:40][C:28]=3[Cl:27])[CH2:36][CH2:35]2)[CH:11]=1)(=[O:5])[CH3:4]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 38646564-(2-Chlorophenoxy)piperidineHCID 11256532N-[6-(2-Acetylaminoethylamino)-2-phenylpyrimidin-4-yl]-2-chloroacetamide

Product 1

HCID 22378755N-[6-(2-Acetylaminoethylamino)-2-phenylpyrimidin-4-yl]-2-[4-(2-chlorophenoxy)-piperidin-1-yl]-acetamide

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium iodide (19 mg; 0.13 mmol) was added to a solution of chloroacetamide 6 (40 mg; 0.12 mmol), piperidine 7.6 (31 mg; 0.15 mmol) and DIPEA (30 μL; 0.17 mmol) in 3:1 acetonitrile:THF (2 mL). After 22 h the reaction was filtered through a short plug of silica gel with THF as a wash. The solution was concentrated in vacuo then purified on silica gel (20 mL) with 10:1 EtOAc:i-PrOH yielding a hard white foam (59.2 mg; 98%). LC (method B) tR=12.9 min; 1H NMR (200 MHz, CDCl3) δ 9.51 (s, 1H), 8.37 (m, 2H), 7.47 (m, 3H), 7.38 (m, 1H), 7.31-7.14 (m, 2H), 7.02-6.86 (m, 2H), 6.72 (brs, 1H), 5.69 (brt, J=5.6 Hz, 1H), 4.48 (m, 1H), 3.67 (m, 2H), 3.53 (m, 2H), 3.19 (s, 2H), 2.90 (m, 2H), 2.56 (m, 2H), 2.20-2.00 (m, 4H), 1.86 (s, 3H). ESIMS 523.0/525.0 (100/42) [MH+], 262 (58), 198 (75).

Workup

  1. filtrationAfter 22 h the reaction was filtered through a short plug of silica gel with THF as a wash
  2. concentrationThe solution was concentrated in vacuo
  3. customthen purified on silica gel (20 mL) with 10:1 EtOAc

Sources & evidence

ORD record
ord-f0bac304d53143b19242f8a5d511f507
Source dataset
uspto-grants-2005_07
Patent number
US06916804B2

Reaction notes

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