Bis-(1H-imidazol-2-YL)-methanone → N-(3-{4-[3-Methyl-4-(pyridin-3-yloxy)-phenylamino]-pyrido[3,4-d]pyrimidin-6-yl}-3-aza-bicyclo[3.1.0]hex-6-yl)-2-methylsulfanyl-acetamide

HRID 584566Notes

Reaction equation

HRID 584566 reaction equation
CC[C:3](O)=[S:4].[C:6]([C:13]1NC=CN=1)(C1NC=CN=1)=[O:7].[NH2:18][CH:19]1[CH:24]2[CH:20]1[CH2:21][N:22]([C:25]1[N:49]=[CH:48][C:28]3[N:29]=[CH:30][N:31]=[C:32]([NH:33][C:34]4[CH:39]=[CH:38][C:37]([O:40][C:41]5[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=5)=[C:36]([CH3:47])[CH:35]=4)[C:27]=3[CH:26]=1)[CH2:23]2>C(Cl)Cl>[CH3:47][C:36]1[CH:35]=[C:34]([NH:33][C:32]2[C:27]3[CH:26]=[C:25]([N:22]4[CH2:21][CH:20]5[CH:24]([CH:19]5[NH:18][C:6](=[O:7])[CH2:13][S:4][CH3:3])[CH2:23]4)[N:49]=[CH:48][C:28]=3[N:29]=[CH:30][N:31]=2)[CH:39]=[CH:38][C:37]=1[O:40][C:41]1[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=1

Participants

5

Reactant 3

HCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 10224262[6-(6-Amino-3-aza-bicyclo[3.1.0]hex-3-yl)-pyrido[3,4-d]pyrimidin-4-yl]-[3-methyl-4-(pyridin-3-yloxy)-phenyl]-amineHCID 178460587HCID 178460587, compound

Product 1

HCID 10301303N-(3-{4-[3-Methyl-4-(pyridin-3-yloxy)-phenylamino]-pyrido[3,4-d]pyrimidin-6-yl}-3-aza-bicyclo[3.1.0]hex-6-yl)-2-methylsulfanyl-acetamideYield 62%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 34 μL (0.39 mmol) of methylthioacetic acid in 1 mL of methylene chloride in a ice/brine bath was added 62.8 mg (0.39 mmol) of carbonyl diimidazole. The mixture was stirred for 15 minutes and 150 mg (0.353 mmol) of [6-(6-amino-3-aza-bicyclo[3.1.0]hex-3-yl)-pyrido[3,4-d]pyrimidin-4-yl]-[3-methyl-4-(pyridin-3-yloxy)-phenyl]-amine was added along with additional methylene chloride to aid stirring. After stirring for 1 hour, the reaction was filtered and the precipitate was washed with methylene chloride and air dried. The solid was recrystallized from methanol/methylene chloride to afford 112 mg (62%) of the title compound. 1H NMR (CDCl3): δ 8.83 (s, 1), 8.35 (s, 1), 8.25 (m, 2), 7.72 (m, 1), 7.62 (m, 1), 7.24 (m, 2), 7.07 (s, 1), 6.91 (d, 1), 3.92 (d, 2), 3.52 (m, 2), 3.13 (s, 2), 2.48 (m, 1), 2.22 (s, 3), 2.10 (s, 3), 1.89 (m, 2), M.S. (m+1): 514. HPLC retention time (minutes): 5.154.

Workup

  1. stirringto aid stirring
  2. stirringAfter stirring for 1 hour
  3. filtrationthe reaction was filtered
  4. washthe precipitate was washed with methylene chloride and air
  5. customdried
  6. customThe solid was recrystallized from methanol/methylene chloride

Sources & evidence

ORD record
ord-0fcaa8a5263f4e36bcd94d4f94aeb06f
Source dataset
uspto-grants-2005_08
Patent number
US06927220B2

Reaction notes

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