Diisopropylethylamine → HCID 56847658, compound

HRID 1465195Notes

Reaction equation

HRID 1465195 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][C:17]=1[F:23].[CH3:24][N:25]([CH3:43])[CH2:26][CH2:27][C:28]1[C:29]([C:40](O)=[O:41])=[N:30][N:31]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[CH:32]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:40]([C:29]2[C:28]([CH2:27][CH2:26][N:25]([CH3:43])[CH3:24])=[CH:32][N:31]([C:33]3[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=3)[N:30]=2)=[O:41])=[CH:18][C:17]=1[F:23]

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 114269974-((6,7-Dimethoxyquinolin-4-yl)oxy)-3-fluorobenzenamineHCID 66611674HCID 66611674, compound

Product 1

HCID 56847658HCID 56847658, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of A2 (50 mg, 0.16 mmol, 1.0 eq), O2 (44 mg, 0.16 mmol, 1.0 eq.) and DIPEA (62 mg, 0.48 mmol, 3.0 eq.) in dry DMF (4 mL) was added HATU (121 mg, 0.32 mmol, 2.0 eq.). The mixture was stirred for 12 h at 60° C. Then the mixture was diluted with EtOAc and washed three times with aq. NaHCO3-solution. The organic phase was dried over MgSO4 and evaporated in vacuo. The residue was purified by reverse phase RP-HPLC (column: C18), using H2O and ACN as eluents. The desired fractions were lyophilized to yield the desired compound O3 with impurities. A subsequent purification by chromatography on silica gel (DCM/MeOH=20:1) yielded the product O3 (15 mg, 0.026 mmol, 16%) as a white solid. 1H NMR (400 MHz, d6-DMSO, 300K) δ 2.34 (s, 6H), 2.72 (m, 2H), 2.98 (t, J=7.4 Hz, 2H), 3.94 (s, 6H), 6.47 (d, J=5.3 Hz, 1H), 7.40 (s, 1H), 7.44 (m, 3H), 7.53 (s, 1H), 7.77 (d, J=8.8 Hz, 1H), 8.03 (m, 3H), 8.48 (d, J=5.3 Hz, 1H), 8.51 (s, 1H), 10.44 (s, 1H). MS (ES) C31H29F2N5O4 requires: 573. Found: 574 (M+H)+.

Workup

  1. washwashed three times with aq. NaHCO3-solution
  2. dry with materialThe organic phase was dried over MgSO4
  3. customevaporated in vacuo
  4. customThe residue was purified by reverse phase RP-HPLC (column: C18)

Sources & evidence

ORD record
ord-4b8cb637dc6a4923a042582eec62f186
Source dataset
uspto-grants-2015_04
Patent number
US08999982B2

Reaction notes

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