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Sodium Carbonate → 6-((3S,4S)-3-(Dimethylamino)-4-hydroxypyrrolidin-1-yl)-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 924106
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HRID 924106 반응식
Cl[C:2]1[C:21]([C:22]2[CH:23]=[N:24][CH:25]=[N:26][CH:27]=2)=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1.CCN(C(C)C)C(C)C.[CH3:37][N:38]([CH3:45])[C@H:39]1[CH2:43][NH:42][CH2:41][C@@H:40]1[OH:44].C([O-])([O-])=O.[Na+].[Na+]>CC(O)C>[CH3:37][N:38]([CH3:45])[C@@H:39]1[C@@H:40]([OH:44])[CH2:41][N:42]([C:2]2[C:21]([C:22]3[CH:27]=[N:26][CH:25]=[N:24][CH:23]=3)=[CH:20][C:5]([C:6]([NH:8][C:9]3[CH:14]=[CH:13][C:12]([O:15][C:16]([F:18])([F:19])[F:17])=[CH:11][CH:10]=3)=[O:7])=[CH:4][N:3]=2)[CH2:43]1
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참가 물질

6

반응물 4

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 45791186(3S,4S)-4-(dimethylamino)pyrrolidin-3-olHCID 722034246-Chloro-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

생성물 1

HCID 899083666-((3S,4S)-3-(Dimethylamino)-4-hydroxypyrrolidin-1-yl)-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

시약·촉매·용매

1
HCID 3776Isopropanol용매

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온도
110 °C

실험 절차

6-Chloro-5-(pyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 223.1, 60 mg, 0.149 mmol) and DIPEA (0.182 mL, 1.043 mmol) were added to a vial containing iPrOH (1 mL). (3S,4S)-4-(Dimethylamino)pyrrolidin-3-ol (50 mg, 0.246 mmol) was added. The mixture was stirred at 110° C. for 16 h. The RM was treated with sat. aq. Na2CO3 (20 mL) and was extracted with EtOAc. The combined extracts were washed with brine (10 mL), dried over Na2SO4, filtered and the filtrate was evaporated off under reduced pressure to give a crude product that was purified by preparative SFC (Column DEAP, from 13% to 18% in 6 min) to afford the title product as a white solid. HPLC (Condition 10) tR=5.62 min, UPLC-MS (Condition 3) tR=0.73 min, m/z=489.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.15 (s, 6H) 2.52-2.59 (m, 1H) 2.87 (dd, J=10.95, 5.08 Hz, 1H) 3.19 (dd, J=11.34, 5.90 Hz, 1H) 3.28 (m, J=11.30, 6.30 Hz, 1H) 3.45 (dd, J=11.34, 6.65 Hz, 1H) 4.08 (quin, J=5.08 Hz, 1H) 5.09 (d, J=5.08 Hz, 1H) 7.36 (d, J=8.60 Hz, 2H) 7.85 (m, J=9.00 Hz, 2H) 8.11 (d, J=2.35 Hz, 1H) 8.80 (d, J=2.35 Hz, 1H) 8.90 (s, 2H) 9.20 (s, 1H) 10.19 (s, 1H).

후처리

  1. extractionwas extracted with EtOAc
  2. washThe combined extracts were washed with brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customthe filtrate was evaporated off under reduced pressure
  6. customto give a crude product that
  7. customwas purified by preparative SFC (Column DEAP, from 13% to 18% in 6 min)

출처 및 근거

ORD 기록
ord-30cf9198b5e64fa0a66442de50112848
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09278981B2

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