Piperidine → HCID 67306163, compound

HRID 1921981Notes

Reaction equation

HRID 1921981 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[C:8]([C:23]3[CH:28]=[CH:27][N:26]=[C:25]([NH:29][CH2:30][C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([O:37][CH3:38])[CH:32]=4)[N:24]=3)[CH:9]=[C:10]2[N:13]2[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][CH2:21]O)[CH2:15][CH2:14]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[NH:51]1[CH2:56][CH2:55][CH2:54][CH2:53][CH2:52]1>ClCCl.O>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6](=[CH:5][CH:4]=1)[CH:7]=[C:8]([C:23]1[CH:28]=[CH:27][N:26]=[C:25]([NH:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([O:37][CH3:38])[CH:32]=3)[N:24]=1)[CH:9]=[C:10]2[N:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][CH2:21][N:51]2[CH2:56][CH2:55][CH2:54][CH2:53][CH2:52]2)[CH2:15][CH2:14]1

Participants

7

Reactant 4

HCID 8082PiperidineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 67306269HCID 67306269, compound

Product 1

HCID 67306163HCID 67306163, compoundYield 24.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 3-(4-(7-methoxy-3-(2-((3-methoxybenzyl)amino)pyrimidin-4-yl)naphthalen-1-yl)piperazin-1-yl)propan-1-ol (65 mg, 0.127 mmol) and triethlyamine (35 μl, 0.254 mmol) in dichloromethane (2 ml) was treated with methanesulfonyl chloride (10 μl, 0.133 mmol) and stirred for one hour. The mixture was diluted with water (2 ml), the organic layer removed and the aqueous layer extracted with dichloromethane (2 ml). The organic layer was concentrated under reduced pressure. The product was treated with acetonitrile (2 ml) and treated with piperidine (38 μl, 0.381 mmol) and heated to 50° C. for 1 hour then concentrated under reduced pressure. The mixture was diluted with saturated aqueous sodium bicarbonate (10 ml) and extracted with dichloromethane (3×10 ml). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure and purified by flash column chromatography using a gradient of methanol-dichloromethane as eluent to afford 4-(6-methoxy-4-(4-(3-(piperidin-1-yl)propyl)piperazin-1-yl)naphthalen-2-yl)-N-(3-methoxybenzyl)pyrimidin-2-amine (194) (18 mg). M.p.=63-75° C.; 400 M Hz 1H NMR (DMSO-d6) δ: 8.35 (d, J=5.2 Hz, 1H), 8.30 (s, 1H), 7.94 (d, J=9.2 Hz, 1H), 7.81 (bm, 2H), 7.42 (s, 1H), 7.23 (m, 3H), 6.99 (bm, 2H), 6.78 (dd, J=2.0 and 8.4 Hz, 1H), 4.55 (d, J=6.4 Hz, 2H), 3.91 (s, 3H), 3.71 (s, 3H), 3.40-2.40 (m, 16H), 1.73 (bm, 2H), 1.57 (bm, 4H), 1.44 (bm, 2H); LCMS: 581 [M+H+].

Workup

  1. customthe organic layer removed
  2. extractionthe aqueous layer extracted with dichloromethane (2 ml)
  3. concentrationThe organic layer was concentrated under reduced pressure
  4. additionThe product was treated with acetonitrile (2 ml)
  5. concentrationthen concentrated under reduced pressure
  6. additionThe mixture was diluted with saturated aqueous sodium bicarbonate (10 ml)
  7. extractionextracted with dichloromethane (3×10 ml)
  8. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-8ace586ef40f463d8971253d185fce89
Source dataset
uspto-grants-2012_05
Patent number
US08173808B2

Reaction notes

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