Diisopropylethylamine → HCID 135938498, compound

HRID 1842852Notes

Reaction equation

HRID 1842852 reaction equation
Cl.Cl.[NH2:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]2[N:10]([CH2:18][C:19]([OH:21])=O)[N:11]=[C:12]([C:13]3[NH:14][CH:15]=[CH:16][N:17]=3)[C:5]=12.Cl.Cl.[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]2[CH2:36][CH2:35][NH:34][C:33]([CH3:38])([CH3:37])[CH2:32]2)=[CH:27][C:26]=1[O:39][CH3:40].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>CN(C=O)C>[NH2:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]2[N:10]([CH2:18][C:19]([N:34]3[CH2:35][CH2:36][N:31]([C:28]4[CH:29]=[CH:30][C:25]([Cl:24])=[C:26]([O:39][CH3:40])[CH:27]=4)[CH2:32][C:33]3([CH3:38])[CH3:37])=[O:21])[N:11]=[C:12]([C:13]3[NH:17][CH:16]=[CH:15][N:14]=3)[C:5]=12

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67183794HCID 67183794, compoundHCID 136335077HCID 136335077, compound

Product 1

HCID 135938498HCID 135938498, compoundYield 45.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

[4-Amino-3-(1H-imidazol-2-yl)pyrazolo[3,4-d]pyrimidin-1-yl]acetic acid dihydrochloride (100 mg, 0.2 mmol) and 1-(4-chloro-3-methoxyphenyl)-3,3-dimethylpiperazine dihydrochloride (100 mg, 0.3 mmol) were suspended in anhydrous DMF (2.5 mL). N,N-Diisopropylethylamine (0.32 mL, 1 mmol) was added at 0° C. and the mixture was stirred at room temperature until all solids dissolved to give a brown solution. HBTU (114 mg, 0.3 mmol) was added. After 2 h, the reaction mixture was poured slowly into a flask of vigorously stirred ice-water (100 mL). The resulting suspension was extracted with dichloromethane (100 mL) and washed with saturated NaHCO3 (100 mL), brine (100 mL) and evaporated. The residue was purified by flash column chromatography to afford 2-[4-amino-3-(1H-imidazol-2-yl)-pyrazolo[3,4-d]pyrimidin-1-yl]-1-[4-(4-chloro-3-methoxyphenyl)-2,2-dimethylpiperazin-1-yl]ethanone as a light tan solid (45 mg) after evaporation and drying in vacuo. 1H NMR (400 MHz, d6-DMSO) δ 10.14 (d, 1H, J=3.6 Hz), 8.16 (s, 1H), 7.95 (d, 1H, d, J=3.6 Hz), 7.24 (s, 1H), 7.15 (s, 1H), 7.14 (d, 1H, J=8.8 Hz), 6.40 (d, 1H, J=2.4 Hz), 6.31 (dd, 1H, J=2.4 and 8.8 Hz), 5.29 (s, 2H), 3.90 (t, 2H, J=5.4 Hz), 3.84 (s, 3H), 3.46 (t, 2H, J=5.4 Hz), 3.30 (s, 2H), 1.38 (s, 6H). MS (ES) m/z 496.1 (M+H+).

Workup

  1. dissolutiondissolved
  2. customto give a brown solution
  3. extractionThe resulting suspension was extracted with dichloromethane (100 mL)
  4. washwashed with saturated NaHCO3 (100 mL), brine (100 mL)
  5. customevaporated
  6. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-9ab0baa5efb34d13a40516115d050f10
Source dataset
uspto-grants-2015_02
Patent number
US08946240B2

Reaction notes

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