Diisopropylethylamine → 6-Benzyl-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine

HRID 657772Notes

Reaction equation

HRID 657772 reaction equation
[CH2:1]([N:8]1[CH2:18][CH2:17][C:11]2[N:12]=[CH:13][N:14]=[C:15](Cl)[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:19][C:20]([F:30])([F:29])[C:21]1[N:26]=[CH:25][C:24]([CH2:27][NH2:28])=[CH:23][CH:22]=1.C(N(CC)C(C)C)(C)C>C(#N)C>[CH2:1]([N:8]1[CH2:18][CH2:17][C:11]2[N:12]=[CH:13][N:14]=[C:15]([NH:28][CH2:27][C:24]3[CH:25]=[N:26][C:21]([C:20]([F:30])([F:19])[F:29])=[CH:22][CH:23]=3)[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27377185-(Aminomethyl)-2-(trifluoromethyl)pyridineHCID 253240466-Benzyl-4-chloro-5,6,7,8-tetrahydropyrido(4,3-d)pyrimidine

Product 1

HCID 598407136-Benzyl-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amineYield 86%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Two 20 mL microwave vials were each charged with a half portion of 6-benzyl-4-chloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (5.62 g, 21.6 mmol), (6-(trifluoromethyl)pyridin-3-yl)methanamine (5.0 g, 28 mmol), N,N-diisopropylethylamine (7.6 mL, 44 mmol) and acetonitrile (10 mL), and the mixture was subjected to a microwave irradiation at 200° C. for 3.5 h. LC-MS analysis showed the reaction was complete for both samples. The samples were combined, and partitioned between CH2Cl2 (150 mL) and 0.5M NaH2PO4 (pH 4; 120 mL). The organic layer was extracted with 2M HCl (60 mL, 30 mL). The combined acid extracts were basified with 50% KOH (25 mL), extracted with CH2Cl2 (2×100 mL), dried (Na2SO4), filtered and concentrated to yield a light brown oil, which was absorbed on silica (40 g) and purified by column (120 g silica gel, 0-7.5% MeOH/CH2Cl2) to afford a light yellow foam (7.42 g, 86%).

Workup

  1. customthe mixture was subjected to a microwave irradiation at 200° C. for 3.5 h
  2. custompartitioned between CH2Cl2 (150 mL) and 0.5M NaH2PO4 (pH 4; 120 mL)
  3. extractionThe organic layer was extracted with 2M HCl (60 mL, 30 mL)
  4. extractionextracted with CH2Cl2 (2×100 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a light brown oil, which
  9. customwas absorbed on silica (40 g)
  10. custompurified by column (120 g silica gel, 0-7.5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-38d7189c8a0f436c8d7e9550f5f23bb6
Source dataset
uspto-grants-2011_12
Patent number
US08076345B2

Reaction notes

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