Hydrochloric Acid → HCID 86712737, compound

HRID 1779108Notes

Reaction equation

HRID 1779108 reaction equation
C(=O)([O-])[O-].[NH4+].[NH4+].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH:17]([N:20]2[CH:24]=[C:23]([NH:25][C:26]3[N:31]=[C:30]([CH2:32][CH2:33][C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=4[CH2:40][C:41](O)=[O:42])[C:29]([C:44]([F:47])([F:46])[F:45])=[CH:28][N:27]=3)[CH:22]=[N:21]2)[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].C1C=CC2N(O)N=[N:54]C=2C=1.CCN=C=NCCCN(C)C.Cl.Cl>CCN(CC)CC.CN(C=O)C>[NH2:54][C:41](=[O:42])[CH2:40][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=1[CH2:33][CH2:32][C:30]1[C:29]([C:44]([F:45])([F:46])[F:47])=[CH:28][N:27]=[C:26]([NH:25][C:23]2[CH:22]=[N:21][N:20]([CH:17]3[CH2:18][CH2:19][N:14]([C:12]([O:11][C:7]([CH3:8])([CH3:9])[CH3:10])=[O:13])[CH2:15][CH2:16]3)[CH:24]=2)[N:31]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 517111Ammonium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86712736HCID 86712736, compound

Product 1

HCID 86712737HCID 86712737, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Ammonium carbonate (903 mg 9.40 mmol) was added to a suspension of 2-(2-(2-(2-((1-(1-(tert-butoxycarbonyl)piperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid (A136) (270 mg, 0.470 mmol), HOBt (317 mg, 2.35 mmol) and EDCl.HCl (450 mg, 2.35 mmol) in Et3N (1.0 mL) and DMF (25 mL) and the resulting solution was stirred at 40° C. overnight. The volatiles were removed in vacuo and the resulting residue was dissolved in EtOAc (250 mL) and washed with water (250 mL). The organics were adsorbed onto silica gel and the product was purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C., then 0-20% MeOH in EtOAc) to yield the title compound (A137) as a white solid (171 mg, 63%). LCMS-A: rt 6.481 min; m/z 574.3 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. dissolutionthe resulting residue was dissolved in EtOAc (250 mL)
  3. washwashed with water (250 mL)
  4. customthe product was purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.

Sources & evidence

ORD record
ord-e7daf44ec32f43439bc760a8631e5df2
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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