Diisopropylethylamine → HCID 136286768, compound

HRID 1476854Notes

Reaction equation

HRID 1476854 reaction equation
Cl.[CH3:2][N:3]([CH3:10])[CH2:4]/[CH:5]=[CH:6]/[C:7](O)=[O:8].[NH:11]1[CH2:15][CH2:14][C@H:13]([O:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[C:19]([C:27]3[NH:31][C:30](=[O:32])[NH:29][N:28]=3)[N:18]=2)[CH2:12]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.CCOC(C)=O>[CH3:2][N:3]([CH3:10])[CH2:4]/[CH:5]=[CH:6]/[C:7]([N:11]1[CH2:15][CH2:14][C@H:13]([O:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[C:19]([C:27]3[NH:31][C:30](=[O:32])[NH:29][N:28]=3)[N:18]=2)[CH2:12]1)=[O:8]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 45358758(2E)-4-(Dimethylamino)-2-butenoic acid hydrochlorideHCID 136596940HCID 136596940, compound

Product 1

HCID 136286768HCID 136286768, compoundYield 47.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (E)-4-(dimethylamino)but-2-enoic acid hydrochloride (23.40 mg, 0.141 mmol), (S)-3-(1-(pyrrolidin-3-yloxy)isoquinolin-3-yl)-1H-1,2,4-triazol-5(4H)-one (100 mg, 0.135 mmol) and HATU (61.4 mg, 0.161 mmol) in DCM (3 mL) was added Hünig's Base (0.070 mL, 0.404 mmol). The reaction mixture was stirred at RT overnight and was subsequently diluted with EtOAc and washed with water. The product remained in the aqueous layer, which was concentrated to afford a residue. The crude product was purified by preparative HPLC eluting with a gradient of 25-50% ACN in water (basic mode). The solvent was removed by lyophilization to give the title compound (26 mg, 47%). 1H NMR (400 MHz, CD3OD) δ ppm 2.33-2.44 (m, 1H), 2.44-2.53 (m, 1H), 2.55 (s, 3H), 2.60 (s, 3H), 3.53 (d, J=6.06 Hz, 1H), 3.59 (d, J=6.57 Hz, 1H), 3.72-3.91 (m, 1H), 3.91-4.00 (m, 2H), 4.14-4.18 (m, 1H), 6.15 (d, J=18.44 Hz, 1H), 6.65-6.89 (m, 2H), 7.58-7.69 (m, 1H), 7.73-7.83 (m, 1H), 7.90 (d, J=3.03 Hz, 1H), 7.96 (d, J=5.31 Hz, 1H), 8.21 (d, J=7.33 Hz, 1H); ESI-MS m/z [M+H]+ 409.5.

Workup

  1. washwashed with water
  2. concentrationwas concentrated
  3. customto afford a residue
  4. customThe crude product was purified by preparative HPLC
  5. washeluting with a gradient of 25-50% ACN in water (basic mode)
  6. customThe solvent was removed by lyophilization

Sources & evidence

ORD record
ord-92c8de6964bc458e94169ae38806a9cc
Source dataset
uspto-grants-2016_08
Patent number
US09402841B2

Reaction notes

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