Hydrochloric Acid → HCID 86712641, compound

HRID 1778971Notes

Reaction equation

HRID 1778971 reaction equation
C1C=CC2N(O)N=[N:7]C=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[C:24]([O:28][C:29]([NH:31][CH2:32][C:33]1[CH:38]=[CH:37][C:36]([NH:39][C:40]2[N:45]=[C:44]([CH2:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=3[CH2:54][C:55]([OH:57])=O)[C:43]([C:58]([F:61])([F:60])[F:59])=[CH:42][N:41]=2)=[CH:35][CH:34]=1)=[O:30])([CH3:27])([CH3:26])[CH3:25].CCN(C(C)C)C(C)C>CN(C=O)C.C1COCC1>[NH2:7][C:55](=[O:57])[CH2:54][C:49]1[CH:50]=[CH:51][CH:52]=[CH:53][C:48]=1[CH2:47][CH2:46][C:44]1[C:43]([C:58]([F:60])([F:59])[F:61])=[CH:42][N:41]=[C:40]([NH:39][C:36]2[CH:37]=[CH:38][C:33]([CH2:32][NH:31][C:29](=[O:30])[O:28][C:24]([CH3:26])([CH3:25])[CH3:27])=[CH:34][CH:35]=2)[N:45]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86712640HCID 86712640, compound

Product 1

HCID 86712641HCID 86712641, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

HOBt (76 mg, 0.56 mmol) and EDCl.HCl (108 mg, 0.561 mmol) were added to a solution of 2-(2-(2-(2-((4-(((tert-butoxycarbonyl)amino)methyl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid (A15) (251 mg, 0.468 mmol) and DIPEA (326 μL, 1.87 mmol) in DMF (2 mL) and THF (10 mL). The resulting mixture was stirred at room temperature overnight then the volatiles were removed in vacuo and the residue partitioned between EtOAc (150 mL) and saturated aqueous NaHCO3 (100 mL). The layers were separated and the organic layer was washed with water (100 mL), brine (50 mL) and dried over MgSO4. The volatiles were removed in vacuo and the residue adsorbed onto silica gel and purified by silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A16 as a tan solid (0.22 g, 89%); 1H NMR (400 MHz, d6-DMSO) δ 10.18 (s, 1H), 8.67 (s, 1H), 7.68 (d, J=8.5 Hz, 2H), 7.43 (s, 1H), 7.33 (t, J=6.0 Hz, 1H), 7.27-7.10 (m, 6H), 6.91 (s, 1H), 3.50 (s, 2H), 3.18 (d, J=5.3 Hz, 2H), 3.14-2.99 (m, 4H), 1.40 (s, 9H). LCMS-A: rt 6.086 min; m/z 530 [M+H]+.

Workup

  1. customthe volatiles were removed in vacuo
  2. customthe residue partitioned between EtOAc (150 mL) and saturated aqueous NaHCO3 (100 mL)
  3. customThe layers were separated
  4. washthe organic layer was washed with water (100 mL), brine (50 mL)
  5. dry with materialdried over MgSO4
  6. customThe volatiles were removed in vacuo
  7. custompurified by silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-d440a57b82ba4d818ebaaf49bec3e5e2
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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