n-(4-Amino-2-fluorophenyl)acetamide → HCID 66610986, compound

HRID 1621790Notes

Reaction equation

HRID 1621790 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[C:4]([F:12])[CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].F[C:24]1[C:29]([C:30]2[N:35]=[C:34]([CH3:36])[N:33]=[C:32]([N:37]([CH2:47][C:48]3[CH:53]=[CH:52][C:51]([O:54][CH3:55])=[CH:50][CH:49]=3)[CH2:38][C:39]3[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=3)[N:31]=2)=[CH:28][C:27]([CH2:56][N:57]2[CH2:62][CH2:61][N:60]([S:63]([CH3:66])(=[O:65])=[O:64])[CH2:59][CH2:58]2)=[CH:26][N:25]=1>C1COCC1>[CH3:55][O:54][C:51]1[CH:50]=[CH:49][C:48]([CH2:47][N:37]([CH2:38][C:39]2[CH:40]=[CH:41][C:42]([O:45][CH3:46])=[CH:43][CH:44]=2)[C:32]2[N:33]=[C:34]([CH3:36])[N:35]=[C:30]([C:29]3[C:24]([NH:1][C:2]4[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[C:4]([F:12])[CH:3]=4)=[N:25][CH:26]=[C:27]([CH2:56][N:57]4[CH2:62][CH2:61][N:60]([S:63]([CH3:66])(=[O:65])=[O:64])[CH2:59][CH2:58]4)[CH:28]=3)[N:31]=2)=[CH:53][CH:52]=1

Participants

5

Reactant 3

HCID 255648n-(4-Amino-2-fluorophenyl)acetamideHCID 2733832Lithium HexamethyldisilazideHCID 666116314-(2-fluoro-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 66610986HCID 66610986, compoundYield 24.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A mixture of N-(4-amino-2-fluorophenyl)acetamide (0.110 g, 0.654 mmol) in THF (5 mL) was cooled to 0° C. under N2. Lithium bis(trimethylsilyl)amide, 1.0 M solution in tetrahydrofuran (Aldrich) (0.636 mL, 3.27 mmol) was added and the mixture was stirred at 0° C. for 30 min before 4-(2-fluoro-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.447 g, 0.720 mmol) was added. The resulting mixture was stirred at 0° C. for 10 min, and then the ice bath was removed and stirring was continued for 2 h. The reaction was quenched with sat. NH4Cl. The resulting mixture was partitioned between pH 7 buffer (1 M TRIS-HCl) and CHCl3. The aqueous layer was extracted with CHCl3 (2×15 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (40 g, 3% MeOH and 12% EtOAc in DCM) to give the product as a yellow solid (0.125 g). m/z (ESI, +ve ion) 770.0 (M+H)+. 1H NMR (300 MHz, CDCl3) δ 11.99 (br. s., 1H); 8.73 (s, 1H); 8.28 (s, 1H); 8.02-8.16 (m, 1H); 7.91 (s, 1H); 7.22 (d, J=7.45 Hz, 5H); 6.96 (d, J=8.33 Hz, 1H); 6.88 (d, J=8.18 Hz, 4H); 4.86 (br. s., 4H); 3.81 (d, J=2.92 Hz, 6H); 3.52 (s, 2H); 3.19 (br. s., 4H); 2.72 (s, 3H); 2.61 (s, 3H); 2.48-2.59 (m, 4H); 2.21 (s, 3H).

Workup

  1. additionwas added
  2. customthe ice bath was removed
  3. stirringstirring
  4. waitwas continued for 2 h
  5. customThe reaction was quenched with sat. NH4Cl
  6. customThe resulting mixture was partitioned between pH 7 buffer (1 M TRIS-HCl) and CHCl3
  7. extractionThe aqueous layer was extracted with CHCl3 (2×15 mL)
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. concentrationconcentrated
  10. customThe crude product was purified by column chromatography (40 g, 3% MeOH and 12% EtOAc in DCM)

Sources & evidence

ORD record
ord-c3154f79a3c04c96923462d049f45957
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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