Diisopropylethylamine → HCID 71735528, compound

HRID 1051997Notes

Reaction equation

HRID 1051997 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=3)[C:15](O)=[O:16])[CH2:9][CH2:8][C:6]=2[N:7]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:54][N:55]1[CH2:60][CH2:59][CH:58]([O:61][C:62]2[CH:68]=[CH:67][C:65]([NH2:66])=[CH:64][CH:63]=2)[CH2:57][CH2:56]1>CN(C=O)C>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[CH2:11][N:10]([C:12]3[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=3)[C:15]([NH:66][C:65]3[CH:64]=[CH:63][C:62]([O:61][CH:58]4[CH2:59][CH2:60][N:55]([CH3:54])[CH2:56][CH2:57]4)=[CH:68][CH:67]=3)=[O:16])[CH2:9][CH2:8][C:6]=2[N:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 167651644-[(1-Methylpiperidin-4-yl)oxy]anilineHCID 866958153-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzoic acid

Product 1

HCID 71735528HCID 71735528, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 3-(2-amino-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzoic acid (41 mg, 0.15 mmol), N,N-diisopropylethylamine (0.105 mL, 0.60 mmol), and HBTU (63 mg, 0.165 mmol) in 1.5 mL DMF was briefly warmed to approx. 50° C. to dissolve solids, then continued stirring at room temperature. After 10 minutes 4-((1-methylpiperidin-4-yl)oxy)aniline (46 mg, 0.225 mmol) was added and the reaction continued at room temperature for 3 hours. The reaction mixture was partitioned between EtOAc and aqueous NaHCO3 solution, the EtOAc layer washed with H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated. The resulting solid was triturated with EtOAc to give the title compound as an off-white solid (48 mg, 70%). 1H NMR (DMSO-d6) δ: 10.02 (s, 1H), 8.13 (s, 1H), 7.60-7.67 (m, 2H), 7.49 (s, 1H), 7.30-7.40 (m, 2H), 7.20 (dt, J=7.7, 2.0 Hz, 1H), 6.90-6.96 (m, 2H), 6.40 (s, 2H), 4.28 (s, 2H), 4.26-4.35 (m, 1H), 3.64 (t, J=5.9 Hz, 2H), 2.77 (t, J=5.9 Hz, 2H), 2.56-2.66 (m, 2H), 2.17 (s, 3H), 2.10-2.21 (m, 2H), 1.86-1.97 (m, 2H), 1.55-1.69 (m, 2H).

Workup

  1. dissolutionto dissolve solids
  2. customThe reaction mixture was partitioned between EtOAc and aqueous NaHCO3 solution
  3. washthe EtOAc layer washed with H2O, brine
  4. dry with materialdried with anhydrous Na2SO4 and rotary evaporated
  5. customThe resulting solid was triturated with EtOAc

Sources & evidence

ORD record
ord-6de0d56fb4124edb939d64c32e313a99
Source dataset
uspto-grants-2016_07
Patent number
US09388176B2

Reaction notes

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