Hydrochloric Acid → HCID 86712704, compound

HRID 1779060Notes

Reaction equation

HRID 1779060 reaction equation
CCN(C(C)C)C(C)C.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20]([C:23]2[CH:28]=[CH:27][C:26]([NH:29][C:30]3N=[C:34]([CH2:36][CH2:37][C:38]4[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:47])([F:46])[F:45])[C:39]=4[CH2:48][C:49](O)=[O:50])[C:33]([C:52]([F:55])([F:54])[F:53])=[CH:32][N:31]=3)=[CH:25][CH:24]=2)[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.C(=O)([O-])[O-].[NH4+:83].[NH4+:84]>CN(C=O)C.O>[NH2:83][C:49](=[O:50])[CH2:48][C:39]1[C:40]([C:44]([F:45])([F:46])[F:47])=[CH:41][CH:42]=[CH:43][C:38]=1[CH2:37][CH2:36][C:34]1[C:33]([C:52]([F:55])([F:53])[F:54])=[CH:32][N:31]=[C:30]([NH:29][C:26]2[CH:27]=[CH:28][C:23]([CH:20]3[CH2:19][CH2:18][N:17]([C:15]([O:14][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:16])[CH2:22][CH2:21]3)=[CH:24][CH:25]=2)[N:84]=1

Participants

9

Reactant 6

HCID 313Hydrochloric Acid2×HCID 757711-Hydroxybenzotriazole2×HCID 81531Diisopropylethylamine2×HCID 517111Ammonium Carbonate2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 86712703HCID 86712703, compound

Product 1

HCID 86712704HCID 86712704, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (0.16 mL, 0.92 mmol) was added to a mixture of 2-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)-6-(trifluoromethyl)phenyl)acetic acid (A96) (0.104 g, 0.160 mmol), HOBt (0.037 g, 0.27 mmol), and EDCl.HCl (0.056 g, 0.29 mmol) in DMF (5.0 mL) under a nitrogen atmosphere. After 15 minutes ammonium carbonate (0.077 g, 0.80 mmol) was added and stirring continued at room temperature for 24 hours. Additional HOBt (0.072 g, 0.53 mmol), EDCl.HCl (0.056 g, 0.29 mmol) and DIPEA (0.16 mL, 0.92 mmol) were added, then and after 15 minutes ammonium carbonate (0.121 g, 1.26 mmol) was also added and the resulting mixture stirred at room temperature for 16 hours. The resulting mixture was diluted with water (20 mL) then extracted with EtOAc (3×20 mL). The combined organic extracts were concentrated under reduced pressure and the residue purified using silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-50% EtOAc in petroleum benzine 40-60° C.) to give the title compound A97 (75 mg, 72%); 1H NMR (400 MHz, d6-DMSO) δ 10.16 (s, 1H), 8.66 (s, 1H), 7.64 (d, J=8.6 Hz, 2H), 7.57 (d, J=7.9 Hz, 1H), 7.51 (d, J=7.4 Hz, 1H), 7.47 (s, 1H), 7.41 (dd, J=7.7, 7.7 Hz, 1H), 7.19 (d, J=8.6 Hz, 2H), 6.96 (s, 1H), 4.07 (m, 2H), 3.74 (s, 2H), 3.09 (m, 4H), 2.79 (m, 2H), 2.62 (m, 1H), 1.74 (m, 2H), 1.49 (m, 2H), 1.42 (s, 9H). LCMS-A: rt 6.63 min; m/z 652.3 [M+H]+.

Workup

  1. stirringthe resulting mixture stirred at room temperature for 16 hours
  2. extractionthen extracted with EtOAc (3×20 mL)
  3. concentrationThe combined organic extracts were concentrated under reduced pressure
  4. customthe residue purified
  5. customsilica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-50% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-ab5bb8ba45cf48478dd3d734b55290d2
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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