Sodium bis(trimethylsilyl)amide → HCID 86647081, compound

HRID 1621966Notes

Reaction equation

HRID 1621966 reaction equation
F[C:2]1[C:7]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([N:15]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)[CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[N:9]=2)=[CH:6][C:5]([C@H:34]([N:36]2[CH2:41][CH2:40][N:39]([S:42]([CH3:45])(=[O:44])=[O:43])[CH2:38][CH2:37]2)[CH3:35])=[CH:4][N:3]=1.[Cl:46][C:47]1[N:52]=[CH:51][C:50]([NH2:53])=[CH:49][C:48]=1[O:54][CH3:55].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[Cl:46][C:47]1[N:52]=[CH:51][C:50]([NH:53][C:2]2[C:7]([C:8]3[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([N:15]([CH2:16][C:17]4[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=4)[CH2:25][C:26]4[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=4)[N:9]=3)=[CH:6][C:5]([C@H:34]([N:36]3[CH2:37][CH2:38][N:39]([S:42]([CH3:45])(=[O:44])=[O:43])[CH2:40][CH2:41]3)[CH3:35])=[CH:4][N:3]=2)=[CH:49][C:48]=1[O:54][CH3:55]

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 234561436-Chloro-5-methoxypyridin-3-amineHCID 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 86647081HCID 86647081, compoundYield 74.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

At 0° C., a solution 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) (155 mg, 0.244 mmol) and 6-chloro-5-methoxypyridin-3-amine (Small Molecules, Inc) (77 mg, 0.488 mmol) in 1 mL of THF was treated with sodium bis(trimethylsilyl)amide (0.853 mL of 1.0 M solution in THF, 0.853 mmol) and the dark red solution was stirred at that temperature for 1 h. It was quenched with 4 mL of saturated aqueous ammonium chloride solution and extracted with EtOAc (2×20 mL). The combined organic phases were washed with brine (10 mL), dried over sodium sulfate, filtered and concentrated. The residue was loaded on a silica gel column and eluted with 50-100% EtOAc in DCM to give the title compound (140 mg, 74% yield) as an orange amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.11 (s, 1H), 8.70 (d, J=2.40 Hz, 1H), 8.37 (d, J=2.30 Hz, 1H), 8.18 (dd, J=8.8, 2.40 Hz, 2H), 7.28 (m, 4H), 6.90 (m, 4H), 4.85-4.81 (m, 4H), 3.87 (s, 3H), 3.74 (s, 3H), 3.70 (s, 3H), 3.60 (m, 1H), 3.04 (m, 4H), 2.78 (s, 3H), 2.59 (s, 3H), 2.47 (m, 4H), 1.34 (m, 3H). m/z (ESI, positive ion) 774.9 (M+H)+.

Workup

  1. customIt was quenched with 4 mL of saturated aqueous ammonium chloride solution
  2. extractionextracted with EtOAc (2×20 mL)
  3. washThe combined organic phases were washed with brine (10 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washeluted with 50-100% EtOAc in DCM

Sources & evidence

ORD record
ord-84b7abf9fc8b41a385f435c980d7d8e4
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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