Sodium Iodide → N-[6-(2-Acetylaminoethylamino)-2-phenylpyrimidin-4-yl]-2-[4-(3-chlorophenoxy)-piperidin-1-yl]-acetamide

HRID 895469Notes

Reaction equation

HRID 895469 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-].[Cl:28][C:29]1[CH:30]=[C:31]([CH:39]=[CH:40][CH:41]=1)[O:32][CH:33]1[CH2:38][CH2:37][NH2+:36][CH2:35][CH2:34]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:36]2[CH2:35][CH2:34][CH:33]([O:32][C:31]3[CH:39]=[CH:40][CH:41]=[C:29]([Cl:28])[CH:30]=3)[CH2:38][CH2:37]2)[CH:11]=1)(=[O:5])[CH3:4]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 11256532N-[6-(2-Acetylaminoethylamino)-2-phenylpyrimidin-4-yl]-2-chloroacetamideHCID 685348514-(3-Chlorophenoxy)-piperidinium chloride

Product 1

HCID 11455234N-[6-(2-Acetylaminoethylamino)-2-phenylpyrimidin-4-yl]-2-[4-(3-chlorophenoxy)-piperidin-1-yl]-acetamide

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

Large scale reaction: Sodium iodide (2.45 g; 16.3 mmol) was added to a suspension of chloroacetamide 6 (5.67 g; 16.3 mmol), piperidinium chloride 7.5 (4.85 g; 19.5 mmol) and DIPEA (7.0 mL; 40.2 mmol) in 3:1 acetonitrile:THF (480 mL). After 19.5 h the reaction was concentrated on a rotary evaporator. EtOAc (250 mL) was added and the suspension was washed with 50% saturated NaHCO3 (1×50 mL), water (2×25 mL) and saturated NaCl (2×35 mL). The orange-brown solution was dried over MgSO4; charcoal (0.86 g) was added and this was filtered then concentrated leaving a light orange foam. The crude material was purified on silica gel (850 mL) with 12-9:1 EtOAc:i-PrOH. Product was obtained as a pale yellow/off-white hard foam (7.82 g; 92%).

Workup

  1. customLarge scale reaction
  2. concentrationAfter 19.5 h the reaction was concentrated on a rotary evaporator
  3. additionEtOAc (250 mL) was added
  4. washthe suspension was washed with 50% saturated NaHCO3 (1×50 mL), water (2×25 mL) and saturated NaCl (2×35 mL)
  5. dry with materialThe orange-brown solution was dried over MgSO4
  6. additioncharcoal (0.86 g) was added
  7. filtrationthis was filtered
  8. concentrationthen concentrated
  9. customleaving a light orange foam
  10. customThe crude material was purified on silica gel (850 mL) with 12-9:1 EtOAc
  11. customProduct was obtained as a pale yellow/off-white hard foam (7.82 g; 92%)

Sources & evidence

ORD record
ord-9500648b9ce04f519f88bf1ed6875b3a
Source dataset
uspto-grants-2005_07
Patent number
US06916804B2

Reaction notes

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