Triethylamine → 1'-(5,7-Difluoro-3-methyl-2-(4-(methylsulfonyl)piperazin-1-yl)quinolin-4-yl)-6'-morpholino-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

HRID 1618760Notes

Reaction equation

HRID 1618760 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4]([N:20]1[C:28]3[C:23](=[N:24][CH:25]=[C:26]([N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)[CH:27]=3)[C:22]3([CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[CH2:21]1)=[C:5]([CH3:19])[C:6]([N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)=[N:7]2.C(N(CC)CC)C.[CH3:47][S:48](Cl)(=[O:50])=[O:49]>C(Cl)Cl>[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4]([N:20]1[C:28]3[C:23](=[N:24][CH:25]=[C:26]([N:29]4[CH2:30][CH2:31][O:32][CH2:33][CH2:34]4)[CH:27]=3)[C:22]3([CH2:35][CH2:36][O:37][CH2:38][CH2:39]3)[CH2:21]1)=[C:5]([CH3:19])[C:6]([N:13]1[CH2:18][CH2:17][N:16]([S:48]([CH3:47])(=[O:50])=[O:49])[CH2:15][CH2:14]1)=[N:7]2

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 672844611'-(5,7-Difluoro-3-methyl-2-(1-piperazinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Product 1

HCID 672849391'-(5,7-Difluoro-3-methyl-2-(4-(methylsulfonyl)piperazin-1-yl)quinolin-4-yl)-6'-morpholino-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1′-(5,7-difluoro-3-methyl-2-(piperazin-1-yl)quinolin-4-yl)-6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (50 mg, 0.093 mmol) in DCM (5.0 mL) was treated with triethylamine (0.019 mL, 0.140 mmol) and methanesulfonyl chloride (7.3 μL, 0.093 mmol) and the reaction was stirred at rt overnight. After this time the reaction was partitioned between EtOAc and water. The separated organic layer was dried over MgSO4 and evaporated in vacuo. Purification by reverse-phase HPLC (10% to 95% acetonitrile in water) gave 1′-(5,7-difluoro-3-methyl-2-(4-(methylsulfonyl)piperazin-1-yl)quinolin-4-yl)-6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine]. 1H NMR (400 MHz, chloroform-d) δ ppm 7.57 (1H, d, J=2.3 Hz), 7.37 (1H, dt, J=9.8, 1.3 Hz), 6.78 (1H, ddd, J=11.8, 9.0, 2.4 Hz), 5.65 (1H, d, J=2.3 Hz), 4.04-4.25 (2H, m), 3.83-3.97 (2H, m), 3.69-3.78 (4H, m), 3.30-3.65 (10H, m), 2.90-3.09 (4H, m), 2.86 (3H, s), 2.26-2.39 (2H, m), 2.25 (3H, s), 1.78 (1H, d, J=13.3 Hz), 1.64-1.75 (1H, m). Mass Spectrum (ESI) m/e=615.3 (M+1).

Workup

  1. customAfter this time the reaction was partitioned between EtOAc and water
  2. dry with materialThe separated organic layer was dried over MgSO4
  3. customevaporated in vacuo
  4. customPurification by reverse-phase HPLC (10% to 95% acetonitrile in water)

Sources & evidence

ORD record
ord-d08645284e494573a35f010ebf552ca3
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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