Diisopropylethylamine → HCID 135869748, compound

HRID 1866581Notes

Reaction equation

HRID 1866581 reaction equation
Cl.Cl.[F:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]([N:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[CH:10]=[CH:11][C:12]=1[Cl:13].[NH:20]1[CH:24]=[CH:23][N:22]=[C:21]1[C:25]1[C:33]2[C:28](=[N:29][CH:30]=[CH:31][CH:32]=2)[N:27]([CH2:34][C:35](O)=[O:36])[N:26]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CCOC(C)=O.CN(C=O)C>[NH:20]1[CH:24]=[CH:23][N:22]=[C:21]1[C:25]1[C:33]2[C:28](=[N:29][CH:30]=[CH:31][CH:32]=2)[N:27]([CH2:34][C:35]([N:17]2[CH2:18][CH2:19][N:14]([C:9]3[CH:10]=[CH:11][C:12]([Cl:13])=[C:7]([O:6][CH2:5][CH2:4][F:3])[CH:8]=3)[CH2:15][CH2:16]2)=[O:36])[N:26]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86618918HCID 86618918, compoundHCID 1361746462-(3-(1H-imidazol-2-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetic acid

Product 1

HCID 135869748HCID 135869748, compoundYield 20%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

To a vial containing 1-(3-(2-fluoroethoxy)-4-chlorophenyl)piperazine dihydrochloride (70 mg, 0.21 mmol) was added 2-(3-(1H-imidazol-2-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetic acid (51 mg, 0.21 mmol), HBTU (83 mg, 0.22 mmol), DMF (0.7 mL), and DIPEA (0.20 mL, 1.2 mmol). The reaction mixture was maintained at 20° C. for 24 h. The solution was diluted with EtOAc (30 mL) and washed with 1N HCl (2×10 mL) and sat. aq. NaCl (2×10 mL). The organic phase was dried over MgSO4 and concentrated in vacuo. The resultant residue was purified by preparative HPLC (20→95% gradient of MeCN—H2O with 0.1% TFA) and the pure fractions lyophilized to afford the indicated compound (20 mg, 20% yield): MS (ES) [M+H]+expected 484.2, found 484.4; 1H NMR (CDCl3, 400 MHz) d 9.94 (br s, 1H), 8.78 (dd, J=1.2, 8, 1H), 8.55 (dd, J=1.2, 4.6, 1H), 7.16-7.26 (m, 4H), 6.45-6.53 (m, 2H), 5.44 (s, 2H), 4.77 (dt, J=4.0, 46.8, 2H), 4.26 (dt, J=4.0, 26.8, 2H), 3.69-3.78 (m, 4H), 3.10-3.21 (m, 4H).

Workup

  1. washwashed with 1N HCl (2×10 mL) and sat. aq. NaCl (2×10 mL)
  2. dry with materialThe organic phase was dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe resultant residue was purified by preparative HPLC (20→95% gradient of MeCN—H2O with 0.1% TFA)

Sources & evidence

ORD record
ord-27df58bd9c61462ea0890941cf0b33bb
Source dataset
uspto-grants-2009_12
Patent number
US07629344B2

Reaction notes

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