6-(2-Fluoropyridin-3-yl)-N-methylpyrimidin-4-amine → HCID 24863500, compound

HRID 2092314Notes

Reaction equation

HRID 2092314 reaction equation
Cl.[CH3:2][C:3]1[CH:12]=[CH:11][C:10]2[C:9]([NH:13][C:14]3[CH:15]=[CH:16][C:17]4[S:21][C:20]([CH3:22])=[N:19][C:18]=4[CH:23]=3)=[N:8][CH:7]=[CH:6][C:5]=2[C:4]=1[NH2:24].F[C:26]1[C:31]([C:32]2[N:37]=[CH:36][N:35]=[C:34]([NH:38][CH3:39])[CH:33]=2)=[CH:30][CH:29]=[CH:28][N:27]=1>>[CH3:2][C:3]1[CH:12]=[CH:11][C:10]2[C:9]([NH:13][C:14]3[CH:15]=[CH:16][C:17]4[S:21][C:20]([CH3:22])=[N:19][C:18]=4[CH:23]=3)=[N:8][CH:7]=[CH:6][C:5]=2[C:4]=1[NH:24][C:26]1[C:31]([C:32]2[CH:33]=[C:34]([NH:38][CH3:39])[N:35]=[CH:36][N:37]=2)=[CH:30][CH:29]=[CH:28][N:27]=1

Participants

3

Reactant 2

HCID 446318726-(2-Fluoropyridin-3-yl)-N-methylpyrimidin-4-amineHCID 67339276HCID 67339276, compound

Product 1

HCID 24863500HCID 24863500, compound

Conditions

Temperature
87 °C

Procedure

6-methyl-N1-(2-methylbenzo[d]thiazol-5-yl)isoquinoline-1,5-diamine hydrochloride (5.94 g, 16.6 mmol) and 6-(2-fluoropyridin-3-yl)-N-methylpyrimidin-4-amine (4.74 g, 23.2 mmol, 1.40 equiv.) were combined in a 350 mL screw-cap pressure tube and flushed with nitrogen. 1M LiHMDS in THF (102 mL) were added in two portions (2×51 mL) at room temperature. The pressure tube was sealed and placed immediately in a pre-heated (87° C.) sonicator bath. The reaction mixture was sonicated at 85° C. for 30 min., cooled to room temperature. The resulting thick suspension was diluted with THF (0.2 L) and quenched into a mixture of sat. aq. NH4Cl (50 mL) and brine (100 mL). The organic layer was separated and concentrated in vacuo with silica (26 g). Column chromatography (CH2Cl2:THF 3:1)—two fractions were collected, the first contained starting material (0.5 L), fraction contained the title compound (2 L). The second fraction was concentrated in vacuo to dryness. The resulting foam was suspended in Et2O (0.12 L) and sonicated until all the material was converted into a homogenous suspension of fine yellow precipitate. 6-Methyl-N5-(3-(6-(methylamino)pyrimidin-4-yl)pyridin-2-yl)-N1-(2-methylbenzo[d]thiazol-5-yl)isoquinoline-1,5-diamine was isolated by filtration as a light yellow powder (2.35 g, 28% yield). MS (M+H)+ 505.

Workup

  1. customscrew-cap pressure tube
  2. customflushed with nitrogen
  3. addition1M LiHMDS in THF (102 mL) were added in two portions (2×51 mL) at room temperature
  4. customThe pressure tube was sealed
  5. customThe reaction mixture was sonicated at 85° C. for 30 min.
  6. temperaturecooled to room temperature
  7. additionThe resulting thick suspension was diluted with THF (0.2 L)
  8. customquenched into a mixture of sat. aq. NH4Cl (50 mL) and brine (100 mL)
  9. customThe organic layer was separated
  10. concentrationconcentrated in vacuo with silica (26 g)
  11. customColumn chromatography (CH2Cl2:THF 3:1)—two fractions were collected
  12. concentrationThe second fraction was concentrated in vacuo to dryness
  13. customsonicated until all the material
  14. additionwas converted into a homogenous suspension of fine yellow precipitate

Sources & evidence

ORD record
ord-6489a9a1cd51494382841d7fc91124df
Source dataset
uspto-grants-2013_05
Patent number
US08440674B2

Reaction notes

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