Acetonitrile → HCID 67306269, compound

HRID 1921997Notes

Reaction equation

HRID 1921997 reaction equation
Cl.Cl.Cl.[CH3:4][O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[CH:12]=[C:11]([C:16]1[CH:21]=[CH:20][N:19]=[C:18]([NH:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([O:30][CH3:31])[CH:25]=3)[N:17]=1)[CH:10]=[C:9]2[N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.Br[CH2:39][CH2:40][CH2:41][OH:42].C(=O)([O-])[O-].[K+].[K+].C(#N)C>O>[CH3:4][O:5][C:6]1[CH:7]=[C:8]2[C:13]([CH:12]=[C:11]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH:22][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([O:30][CH3:31])[CH:25]=4)[N:17]=3)[CH:10]=[C:9]2[N:32]2[CH2:33][CH2:34][N:35]([CH2:39][CH2:40][CH2:41][OH:42])[CH2:36][CH2:37]2)=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 123083-Bromo-1-propanolHCID 67305871HCID 67305871, compound

Product 1

HCID 67306269HCID 67306269, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 4-(6-methoxy-4-(piperazin-1-yl)naphthalen-2-yl)-N-(3-methoxybenzyl)pyrimidin-2-amine tris hydrochloride salt (1.0 g, 1.78 mmol), 3-bromopropan-1-ol (250 mg, 1.80 mmol), potassium carbonate (1.23 g, 8.91 mmol) and acetonitrile (20 ml) was stirred for 16 hours at room temperature. The mixture was diluted with water (100 ml) and extracted with dichloromethane (3×50 ml). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel (24 g) using a gradient of ethyl acetate-hexanes to afford 3-(4-(7-methoxy-3-(2-((3-methoxybenzyl)amino)pyrimidin-4-yl)naphthalen-1-yl)piperazin-1-yl)propan-1-ol 193 as a yellow solid (600 mg, 66%). 400 M Hz 1H NMR (DMSO-d6) δ: 8.35 (d, J=5.2 Hz, 1H), 8.29 (s, 1H), 7.93 (d, J=8.8 Hz, 1H), 7.80 (bm, 2H), 7.42 (s, 1H), 7.23 (m, 3H), 6.99 (bm, 2H), 6.78 (dd, J=2.4 and 8.4 Hz, 1H), 4.55 (m, 3H), 3.91 (s, 3H), 3.71 (s, 3H), 3.50 (m, 3H), 3.06 (bm, 6H), 2.73 (bm, 3H), 1.67 (m, 2H); LCMS[M+H]: 514.

Workup

  1. extractionextracted with dichloromethane (3×50 ml)
  2. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by flash column chromatography on silica gel (24 g)

Sources & evidence

ORD record
ord-449e41b3d658484c903b1fdc12ab9aec
Source dataset
uspto-grants-2012_05
Patent number
US08173808B2

Reaction notes

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