Sodium Iodide → HCID 11548519, compound

HRID 2195050Notes

Reaction equation

HRID 2195050 reaction equation
Cl.Cl[CH2:3][CH2:4][N:5]([CH3:7])[CH3:6].C([O-])([O-])=O.[Cs+].[Cs+].[Cl:14][C:15]1[CH:16]=[C:17]([C:22]2[N:27]=[C:26]([N:28]3[CH2:32][CH2:31][CH2:30][CH:29]3[CH3:33])[N:25]=[C:24]([N:34]3[CH2:39][CH2:38][N:37]([C:40]4[N:45]=[CH:44][C:43]([OH:46])=[CH:42][C:41]=4[CH3:47])[CH2:36][CH2:35]3)[CH:23]=2)[CH:18]=[CH:19][C:20]=1[F:21].[Na+].[I-]>CN(C=O)C>[Cl:14][C:15]1[CH:16]=[C:17]([C:22]2[N:27]=[C:26]([N:28]3[CH2:32][CH2:31][CH2:30][CH:29]3[CH3:33])[N:25]=[C:24]([N:34]3[CH2:35][CH2:36][N:37]([C:40]4[N:45]=[CH:44][C:43]([O:46][CH2:3][CH2:4][N:5]([CH3:7])[CH3:6])=[CH:42][C:41]=4[CH3:47])[CH2:38][CH2:39]3)[CH:23]=2)[CH:18]=[CH:19][C:20]=1[F:21]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 57761731HCID 57761731, compound

Product 1

HCID 11548519HCID 11548519, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled mixture of (2-chloro-ethyl)-dimethyl-amine hydrochloride (116 mg, 0.81 mmol) in DMF, add Cs2CO3 (526 mg, 1.62 mmol) and stir at 0° C. for 30 min. Add 6-{4-[6-(3-chloro-4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-piperazin-1-yl}-5-methyl-pyridin-3-ol (78 mg, 0.16 mmol) and NaI (29 mg, 0.16 mmol). Stir the mixture at room temperature for 1 h and then for 2 h at 45° C. Partition between EtOAc and water. Wash with brine, dry the solution (Na2SO4), and concentrate under reduced pressure. Purify the residue by flash column chromatography eluting with DCM:MeOH:NH4OH (90:10:1) to afford the title compound. 1H NMR (300 MHz, CDCl3): δ1.29 (t, 3H, J=6.3 Hz, CH3); 1.69 (m, 1H, CH2CH2); 1.91 (m, 1H, CH2CH2); 2.05 (m, 2H, CH2CH2); 2.32 (s, 3H, Ar—CH3); 2.33 (s, 6H, N(CH3)2); 2.71 (t, J=5.7 Hz, 2H); 3.13 (m, 4H); 3.64 (m, 4H); 3.80 (m, 4H); 4.06 (t, J=5.7 Hz, 2H); 4.34 (m, 1H); 6.25 (s, 1H, Ar—H); 7.10 (d, J=2.7 Hz, 1H); 7.18 (m, 1H); 7.89 (m, 2H); 8.04 (m, 1H).

Workup

  1. stirringStir the mixture at room temperature for 1 h
  2. waitfor 2 h at 45° C
  3. customPartition between EtOAc and water
  4. washWash with brine
  5. dry with materialdry the solution (Na2SO4)
  6. concentrationconcentrate under reduced pressure
  7. customPurify the residue by flash column chromatography
  8. washeluting with DCM:MeOH:NH4OH (90:10:1)

Sources & evidence

ORD record
ord-1a3eb9096fe649bebfcd8321243fb5a1
Source dataset
uspto-grants-2012_12
Patent number
US08334382B2

Reaction notes

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