Hydrochloric Acid → HCID 86712715, compound

HRID 1779073Notes

Reaction equation

HRID 1779073 reaction equation
C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.CCN(C(C)C)C(C)C.[C:33]([O:37][C:38]([N:40]1[CH2:45][CH2:44][CH:43]([C:46]2[CH:51]=[CH:50][C:49]([NH:52][C:53]3N=[C:57]([CH2:59][CH2:60][C:61]4[CH:66]=[CH:65][C:64]([C:67]([F:70])([F:69])[F:68])=[CH:63][C:62]=4[CH2:71][C:72](O)=[O:73])[C:56]([C:75]([F:78])([F:77])[F:76])=[CH:55][N:54]=3)=[CH:48][CH:47]=2)[CH2:42][CH2:41]1)=[O:39])([CH3:36])([CH3:35])[CH3:34].C(=O)([O-])[O-].[NH4+:83].[NH4+:84]>CN(C=O)C.C1COCC1.CCOC(C)=O>[NH2:83][C:72](=[O:73])[CH2:71][C:62]1[CH:63]=[C:64]([C:67]([F:68])([F:69])[F:70])[CH:65]=[CH:66][C:61]=1[CH2:60][CH2:59][C:57]1[C:56]([C:75]([F:78])([F:76])[F:77])=[CH:55][N:54]=[C:53]([NH:52][C:49]2[CH:48]=[CH:47][C:46]([CH:43]3[CH2:42][CH2:41][N:40]([C:38]([O:37][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:39])[CH2:45][CH2:44]3)=[CH:51][CH:50]=2)[N:84]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 517111Ammonium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86712714HCID 86712714, compound

Product 1

HCID 86712715HCID 86712715, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

HOBt (0.042 g, 0.31 mmol), EDCl.HCl (0.049 g, 0.31 mmol) and DIPEA (0.204 mL, 1.20 mmol) were added to a solution of 2-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)-5-(trifluoromethyl)phenyl)acetic acid (A108) (0.157 g, 0.240 mmol) in dry DMF (5 mL) and dry THF (5 mL). Ammonium carbonate (113 mg, 1.20 mmol) was then added and the resulting mixture was stirred at room temperature for 3 days. The mixture was diluted with EtOAc and washed with 10% aqueous NaHCO3. The organic layer was dried (MgSO4) and the volatiles removed under reduced pressure. The residue was adsorbed onto silica gel and purified by silica gel column chromatography (SiO2, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A109 as a colourless solid (0.121 g, 77%); 1H NMR (400 MHz, d4-MeOH) δ 8.56 (s, 1H), 7.60 (m, 3H), 7.55-7.48 (m, 1H), 7.42 (m, 1H), 7.22 (d, J=8.5 Hz, 2H), 4.23 (d, J=13.3 Hz, 2H), 3.76 (s, 2H), 3.26 (m, 2H), 3.14 (m, 2H), 2.95-2.81 (m, 2H), 2.77-2.64 (m, 1H), 1.83 (m, 2H), 1.70-1.54 (m, 2H), 1.50 (s, 9H). LCMS-A: rt 6.671 min; m/z 652.3 [M+H]+.

Workup

  1. washwashed with 10% aqueous NaHCO3
  2. dry with materialThe organic layer was dried (MgSO4)
  3. customthe volatiles removed under reduced pressure
  4. custompurified by silica gel column chromatography (SiO2, 0-100% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-98a675d59a4e4e6dbfbba1010ad69348
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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