Methanol → 3-{3-[2-({5-fluoro-2-(methyloxy)-4-[2-(1-piperidinyl)ethyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}-N-(2,4,6-trifluorophenyl)benzamide

HRID 419455Notes

Reaction equation

HRID 419455 reaction equation
[F:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[C:5]([F:10])[C:3]=1[NH2:4].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[F:21][C:22]1[C:23]([CH2:56][CH2:57][N:58]2[CH2:63][CH2:62][CH2:61][CH2:60][CH2:59]2)=[CH:24][C:25]([O:54][CH3:55])=[C:26]([NH:28][C:29]2[N:34]=[C:33]([C:35]3[N:39]4[CH:40]=[CH:41][CH:42]=[CH:43][C:38]4=[N:37][C:36]=3[C:44]3[CH:45]=[C:46]([CH:51]=[CH:52][CH:53]=3)[C:47](OC)=[O:48])[CH:32]=[CH:31][N:30]=2)[CH:27]=1.CO>C1COCC1>[F:21][C:22]1[C:23]([CH2:56][CH2:57][N:58]2[CH2:59][CH2:60][CH2:61][CH2:62][CH2:63]2)=[CH:24][C:25]([O:54][CH3:55])=[C:26]([NH:28][C:29]2[N:34]=[C:33]([C:35]3[N:39]4[CH:40]=[CH:41][CH:42]=[CH:43][C:38]4=[N:37][C:36]=3[C:44]3[CH:45]=[C:46]([CH:51]=[CH:52][CH:53]=3)[C:47]([NH:4][C:3]3[C:2]([F:1])=[CH:8][C:7]([F:9])=[CH:6][C:5]=3[F:10])=[O:48])[CH:32]=[CH:31][N:30]=2)[CH:27]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 677652,4,6-TrifluoroanilineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 59452635Methyl 3-{3-[2-({5-fluoro-2-(methyloxy)-4-[2-(1-piperidinyl)ethyl]phenyl]amino)-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl}benzoate

Product 1

HCID 594529013-{3-[2-({5-fluoro-2-(methyloxy)-4-[2-(1-piperidinyl)ethyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}-N-(2,4,6-trifluorophenyl)benzamideYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To 2,4,6-trifluoroaniline (127 mg, 1 mmol) was added 1N NaHMDS in THF (0.9 mL, 0.9 mmol). The mixture stirred for 15 min at rt. Methyl 3-{3-[2-({5-fluoro-2-(methyloxy)-4-[2-(1-piperidinyl)ethyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzoate (Example 128, step A) (100 mg, 0.172 mmol) in 3 mL of dry THF was added. The mixture stirred at rt for 30 minutes. 1 mL of MeOH was added followed by 1 g of silica gel. The solvent was rotovaped down and the pre-adsorbed solids were purified by flash chromatography to give the title compound (74 mg, 0.11 mmol, 62%). 1H NMR (400 MHz, CDCl3) δ ppm 9.44 (d, J=6.96 Hz, 1H), 8.20-8.26 (m, 4H), 7.99 (dt, J=7.83, 1.40 Hz, 1H), 7.74-7.78 (m, 2H), 7.62 (d, J=8.97 Hz, 1H), 7.48 (t, J=7.78 Hz, 1H), 7.31-7.36 (m, 1H), 6.91 (td, J=6.87, 1.28 Hz, 1H), 6.72-6.78 (m, 3H), 6.60 (d, J=5.13 Hz, 1H), 3.90 (s, 3H), 2.78-2.84 (m, 2H), 2.53-2.58 (m, 2H), 2.44-2.53 (m, 4H), 1.58-1.65 (m, J=5.59, 5.59, 5.59, 5.59 Hz, 4H), 1.46 (d, J=5.13 Hz, 2H). MS (ESI): 696 [M+H]+.

Workup

  1. stirringThe mixture stirred at rt for 30 minutes
  2. customthe pre-adsorbed solids were purified by flash chromatography

Sources & evidence

ORD record
ord-54726dd8e3434b1b8dec6794076911ba
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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