Hydrochloric Acid → 4-(5-chloro-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621662Notes

Reaction equation

HRID 1621662 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[NH2:11][C:12]1[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[N:16][CH:17]=1.[Cl:20][C:21]1[CH:22]=[C:23]([C:28]2[N:33]=[C:32]([CH3:34])[N:31]=[C:30]([N:35]([CH2:45][C:46]3[CH:51]=[CH:50][C:49]([O:52][CH3:53])=[CH:48][CH:47]=3)[CH2:36][C:37]3[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=3)[N:29]=2)[C:24](F)=[N:25][CH:26]=1.Cl>C1COCC1.CO>[Cl:20][C:21]1[CH:22]=[C:23]([C:28]2[N:33]=[C:32]([CH3:34])[N:31]=[C:30]([N:35]([CH2:36][C:37]3[CH:38]=[CH:39][C:40]([O:43][CH3:44])=[CH:41][CH:42]=3)[CH2:45][C:46]3[CH:47]=[CH:48][C:49]([O:52][CH3:53])=[CH:50][CH:51]=3)[N:29]=2)[C:24]([NH:11][C:12]2[CH:17]=[N:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)=[N:25][CH:26]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 811216-Methoxy-3-pyridinylamineHCID 2733832Lithium HexamethyldisilazideHCID 666005044-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 666119674-(5-chloro-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineYield 47.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

LiHMDS (1 M in THF, 1250 μL, 1.250 mmol) was added to a solution of 5-amino-2-methoxypyridine (123 mg, 0.990 mmol) and 4-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (190 mg, 0.396 mmol) in THF (5 mL) under nitrogen at rt. A dark orange mixture formed. After 2 h, HCl (5N, 0.3 mL) was added. The mixture was partitioned between EtOAc-water (10 mL each). The aqueous layer was extracted 3× with EtOAc. The combined organic layers were washed with water 3×, NaHCO3 (satd), dried over MgSO4, and concentrated. The residue was purified on silica (10-80% EtOAc in hexane) to give a yellow oil which, upon trituration with MeOH, resulted in a yellow solid (110 mg). LCMS (ES, pos.): calcd for C31H30ClN7O3: 583.2. found: 584.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 11.64 (s, 1H); 8.73 (d, J=2.74 Hz, 1H); 8.25 (d, J=2.54 Hz, 1H); 8.19 (d, J=2.74 Hz, 1H); 7.83 (dd, J=9.00, 2.74 Hz, 1H); 7.19 (dd, J=16.43, 8.61 Hz, 4H); 6.78-6.92 (m, 4H); 6.70 (d, J=8.80 Hz, 1H); 4.86 (s, 2H); 4.81 (s, 2H); 3.92 (s, 3H); 3.80 (d, J=9.19 Hz, 6H); 2.57 (s, 3H).

Workup

  1. customA dark orange mixture formed
  2. customThe mixture was partitioned between EtOAc-water (10 mL each)
  3. extractionThe aqueous layer was extracted 3× with EtOAc
  4. washThe combined organic layers were washed with water 3×, NaHCO3 (satd)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified on silica (10-80% EtOAc in hexane)
  8. customto give a yellow oil which

Sources & evidence

ORD record
ord-b82c16e500c84ae581665fd23fcc9426
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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