6-Methoxy-3-pyridinylamine → HCID 60156086, compound

HRID 1621561Notes

Reaction equation

HRID 1621561 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]([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([S:41]([CH3:44])(=[O:43])=[O:42])=[CH:37][CH:36]=2)=[CH:4][N:3]=1.[NH2:45][C:46]1[CH:47]=[CH:48][C:49]([O:52][CH3:53])=[N:50][CH:51]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.C(Cl)Cl>[CH3:24][O:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][N:15]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[C:10]2[N:9]=[C:8]([C:7]3[C:2]([NH:45][C:46]4[CH:51]=[N:50][C:49]([O:52][CH3:53])=[CH:48][CH:47]=4)=[N:3][CH:4]=[C:5]([CH2:34][C:35]4[CH:40]=[CH:39][C:38]([S:41]([CH3:44])(=[O:42])=[O:43])=[CH:37][CH:36]=4)[CH:6]=3)[N:13]=[C:12]([CH3:14])[N:11]=2)=[CH:18][CH:19]=1

Participants

6

Reactant 3

HCID 811216-Methoxy-3-pyridinylamineHCID 2733832Lithium HexamethyldisilazideHCID 60155988HCID 60155988, compound

Product 1

HCID 60156086HCID 60156086, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

4-(2-Fluoro-5-(4-(methylsulfonyl)benzyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (503 mg, 0.820 mmol) and 5-amino-2-methoxypyridine (112 mg, 0.905 mmol) were dissolved in THF (8.0 mL) and the flask was cooled in an ice water bath while the reaction was stirred under nitrogen. Then, lithium bis(trimethylsilyl)amide (1.0 M solution in tetrahydrofuran (2.5 mL, 2.500 mmol) was added via syringe, and the reaction was stirred for 40 min. Then, the reaction was treated with ice water (0.60 mL) and the reaction was diluted with DCM, dried over sodium sulfate, filtered, concentrated, and purified on a silica gel filter (150 mL fritted filter with about 2 inches of silica gel; DCM to 100:1 DCM/MeOH to 50:1 DCM/MeOH). The pure fractions were set aside, while the impure ones were collected, concentrated, and purified on another silica gel filter (30 mL fritted filter with about 1 inch of silica gel; DCM to 100:1 DCM/MeOH). The fractions with product were combined with the pure fractions from the first column and concentrated to give N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-(4-(methylsulfonyl)benzyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (412 mg). 1H NMR (CDCl3, 400 MHz) δ 11.58 (s, 1H), 8.61 (d, J=2.35 Hz, 1H), 8.26 (d, J=2.54 Hz, 1H), 8.13 (d, J=2.35 Hz, 1H), 7.87 (dd, J=8.90 Hz, 2.64 Hz, 1H), 7.81 (d, J=8.22 Hz, 2H), 7.37 (d, J=8.22 Hz, 2H), 7.21 (d, J=8.61 Hz, 2H), 7.15 (d, J=8.61 Hz, 2H), 6.87 (d, J=8.61 Hz, 2H), 6.82 (d, J=8.41 Hz, 2H), 6.70 (d, J=8.80 Hz, 1H), 4.85 (s, 2H), 4.77 (s, 2H), 4.00 (s, 2H), 3.93 (s, 3H), 3.82 (s, 3H), 3.80 (s, 3H), 2.98 (s, 3H), 2.57 (s, 3H). m/z (ESI, +ve ion) 718 (M+H)+.

Workup

  1. temperaturethe flask was cooled in an ice water bath while the reaction
  2. stirringthe reaction was stirred for 40 min
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified on a silica gel
  7. filtrationfilter (150 mL fritted filter with about 2 inches of silica gel; DCM to 100:1 DCM/MeOH to 50:1 DCM/MeOH)
  8. customwere collected
  9. concentrationconcentrated
  10. custompurified on another silica gel
  11. filtrationfilter (30 mL fritted filter with about 1 inch of silica gel; DCM to 100:1 DCM/MeOH)
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-f6c1d580ad214fbdaf456d40827f189f
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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