Diisopropylethylamine → HCID 136174642, compound

HRID 930598Notes

Reaction equation

HRID 930598 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][C@@H:16]([CH3:20])[CH2:15]2)[CH:10]=[CH:11][C:12]=1[Cl:13].[NH:21]1[CH:25]=[CH:24][N:23]=[C:22]1[C:26]1[C:34]2[C:29](=[N:30][CH:31]=[CH:32][CH:33]=2)[N:28]([CH2:35][C:36](O)=[O:37])[N:27]=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:21]1[CH:25]=[CH:24][N:23]=[C:22]1[C:26]1[C:34]2[C:29](=[N:30][CH:31]=[CH:32][CH:33]=2)[N:28]([CH2:35][C:36]([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][C@@H:16]2[CH3:20])=[O:37])[N:27]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86618919HCID 86618919, compoundHCID 1361746462-(3-(1H-imidazol-2-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)acetic acid

Product 1

HCID 136174642HCID 136174642, compoundYield 13.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
30 °C

Procedure

This compound was prepared by Protocol A. To a vial containing (S)-1-(3-(2-fluoroethoxy)-4-chlorophenyl)-3-methylpiperazine dihydrochloride (80 mg, 0.23 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 (81 mg, 0.21 mmol), DMF (0.7 mL), and DIPEA (0.2 mL, 1.2 mmol). The reaction mixture was maintained at 30° 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 (14 mg, 13% yield): MS (ES) [M+H]+ expected 498.2. found 498.4. 1H NMR (CDCl3, 400 MHz) δ 9.95 (br s, 1H), 8.79 (dd, J=1.6, 8.2, 1H), 8.55 (dd, J=1.6, 4.4, 1H), 7.19-7.26 (m, 4H), 6.44-6.50 (m, 2H), 5.40 (br s, 2H), 4.77 (dt, J=4.2, 47.2, 2H), 4.26 (dt, J=4.2, 27.2, 2H), 2.78-4.42 (m, 10H).

Workup

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

Sources & evidence

ORD record
ord-c385e9f2c2754e09a497d36ad1f5c95f
Source dataset
uspto-grants-2016_03
Patent number
US09296740B2

Reaction notes

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