Acetic Acid → 4-((Benzylamino)methyl)-N-(3-methoxy-4-(6-methylpyridazin-4-yl)phenyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-2-amine

HRID 59167Notes

Reaction equation

HRID 59167 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:16][C:17]2[N:22]=[C:21]([CH:23]=O)[CH:20]=[C:19]([CH2:25][O:26][CH2:27][C:28]([F:31])([F:30])[F:29])[N:18]=2)[CH:6]=[CH:7][C:8]=1[C:9]1[CH:14]=[C:13]([CH3:15])[N:12]=[N:11][CH:10]=1.[CH2:32]([NH2:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.CN(C=O)C.C1COCC1>[CH2:32]([NH:39][CH2:23][C:21]1[CH:20]=[C:19]([CH2:25][O:26][CH2:27][C:28]([F:31])([F:30])[F:29])[N:18]=[C:17]([NH:16][C:5]2[CH:6]=[CH:7][C:8]([C:9]3[CH:14]=[C:13]([CH3:15])[N:12]=[N:11][CH:10]=3)=[C:3]([O:2][CH3:1])[CH:4]=2)[N:22]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 7504BenzylamineHCID 5049666Sodium triacetoxyborohydrideHCID 1178214562-(3-Methoxy-4-(6-methylpyridazin-4-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)-pyrimidine-4-carbaldehyde

Product 1

HCID 863453354-((Benzylamino)methyl)-N-(3-methoxy-4-(6-methylpyridazin-4-yl)phenyl)-6-((2,2,2-trifluoroethoxy)methyl)pyrimidin-2-amine

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-(3-Methoxy-4-(6-methylpyridazin-4-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)-pyrimidine-4-carbaldehyde (100 mg, 0.23 mmol) was dissolved in DCE (4 mL), THF (1 mL) and DMF (0.1 mL). Benzylamine (0.030 mL, 0.28 mmol) and acetic acid (0.013 mL, 0.23 mmol) were added followed by sodium triacetoxyborohydride (69 mg, 0.32 mmol). The mixture was stirred at rt under nitrogen atmosphere for 1 hour. The reaction was quenched with water. The water phase was extracted by DCM (×2). The combined organic layer was dried over anhydrous sodium sulfate and evaporated onto silica. The silica was loaded on a pre-packed silica column. The column was eluted with a gradient of methanol in DCM to give the title compound as a solid, 58 mg (48%).

Workup

  1. customThe reaction was quenched with water
  2. extractionThe water phase was extracted by DCM (×2)
  3. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  4. customevaporated onto silica
  5. washThe column was eluted with a gradient of methanol in DCM

Sources & evidence

ORD record
ord-ccaa09a3a16a4ad3a2443fd1c0297f20
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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