Sodium Carbonate → HCID 89908224, 화합물

HRID 924013

반응식

HRID 924013 반응식
Br[C:2]1[C:3]([N:22]2[CH2:26][CH2:25][C@H:24]([OH:27])[CH2:23]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([Cl:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[N:28]1[CH:33]=[C:32](B(O)O)[CH:31]=[N:30][CH:29]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:20][C:17]([F:19])([F:18])[O:16][C:13]1[CH:14]=[CH:15][C:10]([NH:9][C:7](=[O:8])[C:6]2[CH:21]=[C:2]([C:32]3[CH:33]=[N:28][CH:29]=[N:30][CH:31]=3)[C:3]([N:22]3[CH2:26][CH2:25][C@H:24]([OH:27])[CH2:23]3)=[N:4][CH:5]=2)=[CH:11][CH:12]=1

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 86702602(S)-5-Bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide

생성물 1

HCID 89908224HCID 89908224, 화합물

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

실험 절차

(S)-5-Bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide (Stage 169.1, (116 mg, 0.25 mmol) and pyrimidin-5-ylboronic acid (62 mg, 0.5 mmol) were dissolved in DME (1 mL). A solution of 2 M Na2CO3 (0.375 mL, 0.75 mmol) was added, the mixture was flushed with argon, PdCl2(dppf) (9 mg, 0.013 mmol) was added and the RM subjected to MW irradiation at 100° C. for 2 h. After cooling to RT, the RM was dissolved in EtOAc and washed with brine. The organic phase was dried over Na2SO4 and evaporated under reduced pressure to give a residue that was purified flash chromatography (RediSep® Silica gel column, EtOAc/EtOAc-MeOH (98:2)), from 50% to 100% EtOAc-MeOH (98:2)) and treated with Si-Thiol (80 mg) in MeOH to afford the title compound as a white crystalline powder. HPLC (Condition 4) tR=4.71 min, HPLC Chiral (CHIRALPAK® AD-H, 250×4.6 mm, eluent: EtOH/MeOH (50:50), 0.5 mL/min, UV 210 nm) tR=60.52 min, UPLC-MS (Condition 3) tR=0.95 min, m/z=462.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.68-1.78 (m, 1H) 1.80-1.90 (m, 1H) 2.82-2.92 (m, 1H) 3.15-3.26 (m, 2H) 3.33-3.41 (m, 1H) 4.15-4.24 (m, 1H) 4.86 (d, J=3.52 Hz, 1H) 7.33 (d, J=8.21 Hz, 2H) 7.84 (d, J=9.38 Hz, 2H) 8.03-8.13 (m, 1H) 8.78 (m, J=2.35, 0.78 Hz, 1H) 8.87 (s, 2H) 9.18 (d, J=0.78 Hz, 1H) 10.16 (s, 1H).

후처리

  1. additionwas added
  2. customthe RM subjected to MW irradiation at 100° C. for 2 h
  3. washwashed with brine
  4. dry with materialThe organic phase was dried over Na2SO4
  5. customevaporated under reduced pressure
  6. customto give a residue that
  7. customwas purified flash chromatography (RediSep® Silica gel column, EtOAc/EtOAc-MeOH (98:2))
  8. additionfrom 50% to 100% EtOAc-MeOH (98:2)) and treated with Si-Thiol (80 mg) in MeOH

출처 및 근거

ORD 기록
ord-08ae7d4b8bfc4476af11426ec999ffef
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09278981B2

연결된 노트

불러오는 중…