7-Aminoquinoline → HCID 66611507, compound

HRID 1812302Notes

Reaction equation

HRID 1812302 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].F[C:12]1[C:17]([C:18]2[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([N:25]([CH2:35][C:36]3[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=3)[CH2:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[N:19]=2)=[CH:16][C:15]([C@H:44]([N:46]2[CH2:51][CH2:50][N:49]([S:52]([CH3:55])(=[O:54])=[O:53])[CH2:48][CH2:47]2)[CH3:45])=[CH:14][N:13]=1.[N:56]1[C:65]2[C:60](=[CH:61][CH:62]=[C:63]([NH2:66])[CH:64]=2)[CH:59]=[CH:58][CH:57]=1>C1COCC1>[CH3:34][O:33][C:30]1[CH:29]=[CH:28][C:27]([CH2:26][N:25]([CH2:35][C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)[C:20]2[N:21]=[C:22]([CH3:24])[N:23]=[C:18]([C:17]3[C:12]([NH:66][C:63]4[CH:64]=[C:65]5[C:60]([CH:59]=[CH:58][CH:57]=[N:56]5)=[CH:61][CH:62]=4)=[N:13][CH:14]=[C:15]([C@H:44]([N:46]4[CH2:51][CH2:50][N:49]([S:52]([CH3:55])(=[O:53])=[O:54])[CH2:48][CH2:47]4)[CH3:45])[CH:16]=3)[N:19]=2)=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 113777-AminoquinolineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 66611822(R)-4-(2-fluoro-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 66611507HCID 66611507, compoundYield 101.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Sodium bis(trimethylsilyl)amide (1.0 M in THF) (Aldrich, St. Louis, Mo.; 0.863 mL, 0.863 mmol) was added to a mixture of (R)-4-(2-fluoro-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (Example 146, Step 6; 156.7 mg, 0.246 mmol) and quinolin-7-amine (Ark Pharm, Libertyville, Ill.; 71.1 mg, 0.493 mmol) in THF (2.5 mL) at 0° C., and the resulting dark brown solution was stirred at 0° C. for 2 h. Excess sodium bis(trimethylsilyl)amide was then quenched with saturated aqueous NH4Cl (2 mL), and the reaction mixture was partitioned between EtOAc (50 mL) and saturated aqueous NH4Cl (20 mL). The organic layer was separated, and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic extracts were sequentially washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0 to 6% MeOH/CH2Cl2) furnished (R)-N-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-2-yl)quinolin-7-amine (189 mg, 0.249 mmol, 101% yield) as a yellow-orange foam, which was used directly in Step 2. m/z (ESI, +ve) 760.3 (M+H)+.

Workup

  1. customExcess sodium bis(trimethylsilyl)amide was then quenched with saturated aqueous NH4Cl (2 mL)
  2. customthe reaction mixture was partitioned between EtOAc (50 mL) and saturated aqueous NH4Cl (20 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×20 mL)
  5. washThe combined organic extracts were sequentially washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customChromatographic purification of the residue (silica gel, 0 to 6% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-b0e83ddc09cf4302946b0b6fdbb28ed8
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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