Diisopropylethylamine → HCID 178480919, compound

HRID 2203289Notes

Reaction equation

HRID 2203289 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]([OH:11])=O)[CH2:4][CH2:3]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.[NH2:45][C:46]1[CH:51]=[CH:50][C:49]([CH:52]2[CH2:66][N:56]3[C:57](=[O:65])[NH:58][C:59]4[CH:60]=[CH:61][CH:62]=[CH:63][C:64]=4[C:55]3=[N:54][CH2:53]2)=[CH:48][CH:47]=1>CN(C=O)C>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([CH2:8][C:9]([NH:45][C:46]2[CH:51]=[CH:50][C:49]([CH:52]3[CH2:66][N:56]4[C:57](=[O:65])[NH:58][C:59]5[CH:60]=[CH:61][CH:62]=[CH:63][C:64]=5[C:55]4=[N:54][CH2:53]3)=[CH:48][CH:47]=2)=[O:11])[CH2:6][CH2:7]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 2762732(4-Methylpiperazin-1-yl)acetic acidHCID 178507413HCID 178507413, compound

Product 1

HCID 178480919HCID 178480919, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (4-Methyl-piperazin-1-yl)-acetic acid (3.2 mg, 0.020 mmol), N,N-diisopropylethylamine (0.017 mL, 0.10 mmol), and HBTU (9.1 mg, 0.024 mmol) in 0.6 mL DMF was stirred at rt for 10 minutes, then 3-(4-aminophenyl)-2,3,4,7-tetrahydro-6H-pyrimido[1,2-c]quinazolin-6-one (7.6 mg, 0.026 mmol) added and the reaction continued at rt. At 1.75 hours the reaction mixture was partitioned between EtOAc and aqueous Na2CO3 solution, the EtOAc layer washed with H2O, brine, dried with anhydrous Na2SO4 and rotary evaporated to an oily solid. The residue was chromatographed eluting with 10% MeOH/CHCl3 containing Et3N. The obtained oily solid was then partitioned between EtOAc and aqueous Na2CO3 solution, the EtOAc layer washed with H2O, brine, dried with anhydrous Na2SO4 and evaporated to give the title compound as a white solid (4.8 mg, 73%). 1H NMR (CDCl3) δ: 9.14 (s, 1H), 8.99 (br. s, 1H), 8.11 (d, J=7.9 Hz, 1H), 7.58 (d, J=8.2 Hz, 2H), 7.38-7.44 (m, 1H), 7.22-7.27 (m, 2H), 7.12 (t, J=7.6 Hz, 1H), 6.91 (d, J=8.2 Hz, 1H), 4.53 (dt, J=13.1, 3.6 Hz, 1H), 3.95 (dt, J=16.2, 3.6 Hz, 1H), 3.53-3.69 (m, 2H), 3.15 (s, 2H), 3.00-3.12 (m, 1H), 2.67 (br. s, 4H), 2.52 (br. s, 4H), 2.33 (s, 3H).

Workup

  1. customcontinued at rt
  2. customAt 1.75 hours the reaction mixture was partitioned between EtOAc and aqueous Na2CO3 solution
  3. washthe EtOAc layer washed with H2O, brine
  4. dry with materialdried with anhydrous Na2SO4
  5. customrotary evaporated to an oily solid
  6. customThe residue was chromatographed
  7. washeluting with 10% MeOH/CHCl3
  8. additioncontaining Et3N
  9. customThe obtained oily solid was then partitioned between EtOAc and aqueous Na2CO3 solution
  10. washthe EtOAc layer washed with H2O, brine
  11. dry with materialdried with anhydrous Na2SO4
  12. customevaporated

Sources & evidence

ORD record
ord-ab6ac2dad8f449b592a3099f85f53afd
Source dataset
uspto-grants-2016_06
Patent number
US09365575B2

Reaction notes

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