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

HRID 1779007ノート

反応式

HRID 1779007 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:33]([O:37][C:38]([N:40]1[CH2:45][CH2:44][CH:43]([C:46]2[N:51]=[CH:50][C:49]([NH:52][C:53]3[N:58]=[C:57]([CH2:59][CH2:60][C:61]4[CH:66]=[CH:65][CH:64]=[CH:63][C:62]=4[CH2:67][C:68]([OH:70])=O)[C:56]([C:71]([F:74])([F:73])[F:72])=[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+].[NH4+]>CN(C=O)C>[NH2:7][C:68](=[O:70])[CH2:67][C:62]1[CH:63]=[CH:64][CH:65]=[CH:66][C:61]=1[CH2:60][CH2:59][C:57]1[C:56]([C:71]([F:74])([F:72])[F:73])=[CH:55][N:54]=[C:53]([NH:52][C:49]2[CH:48]=[CH:47][C:46]([CH:43]3[CH2:44][CH2:45][N:40]([C:38]([O:37][C:33]([CH3:34])([CH3:36])[CH3:35])=[O:39])[CH2:41][CH2:42]3)=[N:51][CH:50]=2)[N:58]=1

参加物

8

反応物 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 517111Ammonium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 867126622-(2-(2-(2-((6-(1-(tert-Butoxycarbonyl)piperidin-4-yl)pyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid

生成物 1

HCID 86712663tert-Butyl 4-(5-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

HOBt (50 mg, 0.37 mmol), EDCl.HCl (78 mg, 0.41 mmol) and DIPEA (0.11 mL, 0.63 mmol) were added to a stirred solution of 2-(2-(2-(2-((6-(1-(tert-butoxycarbonyl)piperidin-4-yl)pyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid (A46) (74 mg, 0.13 mmol) in dry DMF (5 mL) under an atmosphere of nitrogen. After 10 minutes ammonium carbonate (121 mg, 1.26 mmol) was added in one portion and the resulting mixture was stirred for 18 hours at room temperature. The volatiles were removed in vacuo and the residue was partitioned between EtOAc (10 mL) and saturated aqueous NaHCO3 (10 mL). The aqueous layer was extracted with EtOAc (2×10 mL) then the combined organic layers were washed with brine (10 mL) and dried over Na2SO4. The volatiles were removed in vacuo and the residue purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridges, 0-100% EtOAc in petroleum benzine 40-60° C. followed by 0-25% MeOH in EtOAc) to give the title compound A47 as clear oil (58 mg, 78%); 1H NMR (400 MHz, CDCl3) δ 8.83 (s, 1H), 8.54 (s, 1H), 7.97 (s, 1H), 7.80 (s, 1H), 7.30-7.22 (m, 4H), 7.17 (d, J=8.5 Hz, 1H), 5.78 (s, 1H), 5.62 (s, 1H), 4.25 (s, 2H), 3.74 (s, 2H), 3.11 (s, 4H), 2.83 (m, 3H), 1.92 (d, J=12.3 Hz, 2H), 1.79-1.60 (m, 2H, peak obscured), 1.48 (s, 9H). LCMS-A: rt 5.549 min; m/z 585 [M+H]+.

後処理

  1. customThe volatiles were removed in vacuo
  2. customthe residue was partitioned between EtOAc (10 mL) and saturated aqueous NaHCO3 (10 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  4. washthe combined organic layers were washed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. customThe volatiles were removed in vacuo
  7. customthe residue purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridges, 0-100% EtOAc in petroleum benzine 40-60° C. followed by 0-25% MeOH in EtOAc)

出典と根拠

ORDレコード
ord-ba203d40843143feba38cdf2741f7d39
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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