4-Aminopyridine → 1-{4-[4-(3,6-dihydro-2H-pyran-4-yl)-6-morpholin-4-yl-[1,3,5]triazin-2-yl]-phenyl}-3-pyridin-4-yl-urea

HRID 404458Notes

Reaction equation

HRID 404458 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[O:13]1[CH2:18][CH:17]=[C:16]([C:19]2[N:24]=[C:23]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[N:22]=[C:21]([C:31]3[CH:36]=[CH:35][C:34]([NH2:37])=[CH:33][CH:32]=3)[N:20]=2)[CH2:15][CH2:14]1.[NH2:38][C:39]1[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=1.CCN(CC)CC>C(Cl)Cl>[O:13]1[CH2:14][CH:15]=[C:16]([C:19]2[N:24]=[C:23]([N:25]3[CH2:26][CH2:27][O:28][CH2:29][CH2:30]3)[N:22]=[C:21]([C:31]3[CH:36]=[CH:35][C:34]([NH:37][C:5]([NH:38][C:39]4[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=4)=[O:11])=[CH:33][CH:32]=3)[N:20]=2)[CH2:17][CH2:18]1

Participants

6

Reactant 4

HCID 17274-AminopyridineHCID 8471TriethylamineHCID 94429TriphosgeneHCID 579682504-[4-(3,6-dihydro-2H-pyran-4-yl)-6-morpholin-4-yl-[1,3,5]triazin-2-yl]-phenylamine

Product 1

HCID 445125731-{4-[4-(3,6-dihydro-2H-pyran-4-yl)-6-morpholin-4-yl-[1,3,5]triazin-2-yl]-phenyl}-3-pyridin-4-yl-ureaYield 34.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of triphosgene (140 mg, 0.47 mmol) in CH2Cl2 (6 mL) was added 4-[4-(3,6-dihydro-2H-pyran-4-yl)-6-morpholin-4-yl-[1,3,5]triazin-2-yl]-phenylamine (200 mg, 0.59 mmol) at 25° C. The reaction mixture was stirred for 15 min and 4-aminopyridine (166 mg, 1.77 mmol) and NEt3 (814 μL, 5.89 mmol) were added and the reaction mixture was stirred for additional 1 hr. The solvents were distilled and the crude mixture was purified by semi-prep-HPLC (TFA-method) to give 1-{4-[4-(3,6-dihydro-2H-pyran-4-yl)-6-morpholin-4-yl-[1,3,5]triazin-2-yl]-phenyl}-3-pyridin-4-yl-urea (75 mg, 22% yield); MS (ESI) m/z 460

Workup

  1. stirringthe reaction mixture was stirred for additional 1 hr
  2. distillationThe solvents were distilled
  3. customthe crude mixture was purified by semi-prep-HPLC (TFA-method)

Sources & evidence

ORD record
ord-274dd69d14bf4045a29af8ded586ae0d
Source dataset
uspto-grants-2014_06
Patent number
US08748421B2

Reaction notes

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