Hydrochloric Acid → tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzoyl)piperazine-1-carboxylate

HRID 1778983ノート

反応式

HRID 1778983 の反応式
C1C=CC2N(O)N=[N:7]C=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.CCN(C(C)C)C(C)C.C[O:34][C:35](=O)[CH2:36][C:37]1[CH:76]=[CH:75][CH:74]=[CH:73][C:38]=1[CH2:39][CH2:40][C:41]1[C:46]([C:47]([F:50])([F:49])[F:48])=[CH:45][N:44]=[C:43]([NH:51][C:52]2[CH:72]=[CH:71][C:55]([C:56]([N:58]3[CH2:63][CH2:62][N:61]([C:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])[CH2:60][CH2:59]3)=[O:57])=[CH:54][CH:53]=2)[N:42]=1.C(=O)([O-])[O-].[NH4+].[NH4+]>C1COCC1.CN(C=O)C>[NH2:7][C:35](=[O:34])[CH2:36][C:37]1[CH:76]=[CH:75][CH:74]=[CH:73][C:38]=1[CH2:39][CH2:40][C:41]1[C:46]([C:47]([F:50])([F:48])[F:49])=[CH:45][N:44]=[C:43]([NH:51][C:52]2[CH:72]=[CH:71][C:55]([C:56]([N:58]3[CH2:59][CH2:60][N:61]([C:64]([O:66][C:67]([CH3:68])([CH3:69])[CH3:70])=[O:65])[CH2:62][CH2:63]3)=[O:57])=[CH:54][CH:53]=2)[N:42]=1

参加物

9

反応物 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 517111Ammonium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86712648tert-Butyl 4-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzoyl)piperazine-1-carboxylate

生成物 1

HCID 86712649tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzoyl)piperazine-1-carboxylate

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

HOBt (0.068 g, 0.50 mmol), EDCl.HCl (0.096 g, 0.50 mmol) and DIPEA (0.34 mL, 1.9 mmol) were added to a stirred solution of tert-butyl 4-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzoyl)piperazine-1-carboxylate (A25) (0.28 g, 0.39 mmol) in dry THF (6 mL) and dry DMF (1 mL) under an atmosphere of nitrogen. After 10 minutes ammonium carbonate (0.19 g, 1.9 mmol) was added in one portion and the resulting solution was stirred at room temperature for 17 hours. The volatiles were removed in vacuo and the residue was partitioned between EtOAc (65 mL) and saturated aqueous NaHCO3 (65 mL). The aqueous layer was extracted with EtOAc (2×50 mL) then the combined organic layers were washed with brine (50 mL) and dried over MgSO4. The volatiles were removed in vacuo and the residue was purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. then 0-20% MeOH in EtOAc) to give the title compound A26 as a white solid (0.18 g, 77%); 1H NMR (400 MHz, CDCl3) δ 8.58 (s, 1H), 7.91 (s, 1H), 7.72 (d, J=8.4 Hz, 2H), 7.44 (d, J=8.3 Hz, 2H), 7.31-7.21 (m, obscured), 5.43 (br. s, 2H), 3.74 (s, 2H), 3.71-3.35 (m, 8H), 3.18-3.03 (m, 4H), 1.47 (s, 9H). LCMS-A: rt 6.120 min; m/z 613.3 [M+H]+.

後処理

  1. customThe volatiles were removed in vacuo
  2. customthe residue was partitioned between EtOAc (65 mL) and saturated aqueous NaHCO3 (65 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  4. washthe combined organic layers were washed with brine (50 mL)
  5. dry with materialdried over MgSO4
  6. customThe volatiles were removed in vacuo
  7. customthe residue was purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.

出典と根拠

ORDレコード
ord-979bc97117f74c28b458b2ab142afbe4
出典データセット
uspto-grants-2016_02
特許番号
US09266864B2

反応ノート

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