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 1779007노트

반응식

HRID 1779007 반응식
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

참가 물질

8

반응물 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

생성물 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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-ba203d40843143feba38cdf2741f7d39
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09266864B2

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