Diisopropylethylamine → (R)-5-bromo-2-(4-(1-(6-(trifluoromethyl)pyridin-3-yl)ethylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzonitrile

HRID 657779Notes

Reaction equation

HRID 657779 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]1[N:8]=[CH:7][C:6]([C@H:9]([NH:11][C:12]2[C:13]3[CH2:21][NH:20][CH2:19][CH2:18][C:14]=3[N:15]=[CH:16][N:17]=2)[CH3:10])=[CH:5][CH:4]=1.[Br:24][C:25]1[CH:26]=[CH:27][C:28](F)=[C:29]([CH:32]=1)[C:30]#[N:31].C(N(CC)C(C)C)(C)C>C(#N)C>[Br:24][C:25]1[CH:26]=[CH:27][C:28]([N:20]2[CH2:19][CH2:18][C:14]3[N:15]=[CH:16][N:17]=[C:12]([NH:11][C@@H:9]([C:6]4[CH:7]=[N:8][C:3]([C:2]([F:1])([F:22])[F:23])=[CH:4][CH:5]=4)[CH3:10])[C:13]=3[CH2:21]2)=[C:29]([CH:32]=1)[C:30]#[N:31]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27249005-Bromo-2-fluorobenzonitrile3×HCID 59840692(R)-N-(1-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine

Product 1

HCID 25062140(R)-5-bromo-2-(4-(1-(6-(trifluoromethyl)pyridin-3-yl)ethylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzonitrileYield 54.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of (R)—N-(1-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine (300 mg, 0.93 mmol), 5-bromo-2-fluorobenzonitrile (560 mg, 2.8 mmol), N,N-diisopropylethylamine (480 μL, 2.8 mmol), and acetonitrile (4 mL) was subjected to microwave irradiation at 180° C. for 2 h. More 5-bromo-2-fluorobenzonitrile (500 mg) was added and the mixture was subjected to microwave irradiation at 180° C. for another 2 h. Additional 5-bromo-2-fluorobenzonitrile (500 mg) was added and the mixture was subjected to microwave irradiation at 180° C. for an additional 2 h. LC-MS indicated the amine was nearly completely consumed. After cooling the mixture was concentrated in vacuo, and the residue was purified by silica gel column (100% EtOAc) to yield a light yellow solid (255 mg, 54%).

Workup

  1. customirradiation at 180° C. for 2 h
  2. customirradiation at 180° C. for another 2 h
  3. customirradiation at 180° C. for an additional 2 h
  4. customwas nearly completely consumed
  5. temperatureAfter cooling the mixture
  6. concentrationwas concentrated in vacuo
  7. customthe residue was purified by silica gel column (100% EtOAc)

Sources & evidence

ORD record
ord-e4e1e0296c744f398f86cc0cdd50cccf
Source dataset
uspto-grants-2011_12
Patent number
US08076345B2

Reaction notes

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