Sodium Iodide → HCID 22353258, compound

HRID 895474Notes

Reaction equation

HRID 895474 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].[F:27][C:28]([F:44])([F:43])[C:29]1[CH:30]=[C:31]([CH:40]=[CH:41][CH:42]=1)[CH2:32][N:33]1[CH2:39][CH2:38][CH2:37][NH: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[CH2:37][CH2:38][CH2:39][N:33]([CH2:32][C:31]3[CH:40]=[CH:41][CH:42]=[C:29]([C:28]([F:43])([F:44])[F:27])[CH:30]=3)[CH2:34][CH2:35]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 22353281Hexahydro-1-[[3-(trifluoromethyl)phenyl]methyl]-1H-1,4-diazepine

Product 1

HCID 22353258HCID 22353258, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium iodide (903 mg; 6.02 mmol) was added to a solution of chloroacetamide 6 (2.088 g; 6.00 mmol), 1-(3-trifluoromethylbenzyl)-[1,4]diazepane (7.40) (1.863 g; 7.21 mmol) and DIPEA (1.45 mL; 8.32 mmol) in 3:1 acetonitrile:THF (30 mL). After 21 h the reaction was concentrated on a rotary evaporator. EtOAc (90 mL) was added and the suspension was washed with 50% saturated NaHCO3 (25 mL), water (3×25 mL) and saturated NaCl (2×25 mL). The solution was dried (MgSO4), filtered, concentrated to an oil then purified on silica gel (340 mL), eluting with 9:1 EtOAc:methanol. Pure product was obtained as a hard white foam (3.10 g; 91%). LC (method B) tR=12.6 min; 1H NMR (200 MHz, CDCl3) δ 9.64 (s, 1H), 8.36 (m, 2H), 7.7-7.3 (m, 7H), 7.22 (s, 1H), 6.56 (brs, 1H), 5.42 (brt, J=5.8 Hz, 1H), 3.75 (s, 2H), 3.68 (m, 2H), 3.54 (m, 2H), 3.32 (s, 2H), 3.0-2.7 (m, 8H), 1.93 (m, 2H), 1.65 (s, 3H). ESIMS 570 (12) [MH+], 286 (100).

Workup

  1. concentrationAfter 21 h the reaction was concentrated on a rotary evaporator
  2. additionEtOAc (90 mL) was added
  3. washthe suspension was washed with 50% saturated NaHCO3 (25 mL), water (3×25 mL) and saturated NaCl (2×25 mL)
  4. dry with materialThe solution was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated to an oil
  7. customthen purified on silica gel (340 mL)
  8. washeluting with 9:1 EtOAc
  9. customPure product was obtained as a hard white foam (3.10 g; 91%)

Sources & evidence

ORD record
ord-234b4f99a11b4056a8de06c6a3aee0bd
Source dataset
uspto-grants-2005_07
Patent number
US06916804B2

Reaction notes

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