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Cesium carbonate → methyl 4-{(3R)-3-[({[3-(trifluoromethyl)benzoyl]amino}acetyl)amino]-1,3'-bipyrrolidin-1'-yl}benzoate

HRID 562584
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HRID 562584 반응식
[N:1]1([CH:23]2[CH2:27][CH2:26][NH:25][CH2:24]2)[CH2:5][CH2:4][C@@H:3]([NH:6][C:7](=[O:22])[CH2:8][NH:9][C:10](=[O:21])[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[CH2:2]1.Br[C:29]1[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].ClCCl>[F:18][C:17]([F:20])([F:19])[C:13]1[CH:12]=[C:11]([CH:16]=[CH:15][CH:14]=1)[C:10]([NH:9][CH2:8][C:7]([NH:6][C@@H:3]1[CH2:4][CH2:5][N:1]([CH:23]2[CH2:27][CH2:26][N:25]([C:29]3[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=3)[CH2:24]2)[CH2:2]1)=[O:22])=[O:21]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 12081Methyl 4-bromobenzoateHCID 516892Sodium BicarbonateHCID 67006850N-{2-[(3R)-1,3'-bipyrrolidin-3-ylamino]-2-oxoethyl}-3-(trifluoromethyl)benzamide

생성물 1

HCID 16666601methyl 4-{(3R)-3-[({[3-(trifluoromethyl)benzoyl]amino}acetyl)amino]-1,3'-bipyrrolidin-1'-yl}benzoate수율 30%

시약·촉매·용매

3
HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매HCID 6344Dichloromethane용매

실험 절차

A slurry of N-{2-[(3R)-1,3′-bipyrrolidin-3-ylamino]-2-oxoethyl}-3-(trifluoromethyl)benzamide (50 mg, 0.13 mmol), methyl 4-bromobenzoate (35 mg, 0.16 mmol), Pd2(dba)3 (12 mg, 0.013 mmol), cesium carbonate (64 mg, 0.19 mmol) and R-BINAP (8 mg, 0.013 mmol) in toluene was heated at 100° C. overnight. To the mixture was added NaHCO3 (sat. aq., 10 mL) and dichloromethane (10 mL). The organic layer was separated and the aqueous layer was washed with an addition portion of dichloromethane (10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The resulting crude product was subjected to flash chromatography (15% MeOH, 1% NH4OH in EtOAc) to afford, as a mixture of diastereomers, methyl 4-{(3R)-3-[({[3-(trifluoromethyl)benzoyl]amino}acetyl)amino]-1,3′-bipyrrolidin-1′-yl}benzoate (20 mg, 30%) as a white solid. 1H-NMR (CDCl3) δ: 1.60-1.76 (m, 1H), 1.86-2.04 (m, 1H), 2.08-2.25 (m, 1H), 2.20-2.44 (m, 2H), 2.60-2.78 (m, 2H), 2.84-3.00 (m, 2H), 3.18 (q, J=8.7 Hz, 1H), 3.32 (q, J=7.5 Hz, 1H), 3.40-3.54 (m, 2H), 3.82 (s, 3H), 4.10 (m, 2H), 4.40-4.56 (m, 1H), 6.44 (d, J=8.7 Hz, 2H), 6.54 (d, J=2.4 Hz, 1H), 7.20-7.35 (m, 1H), 7.54 (t, J=7.8 Hz, 1H), 7.74 (d, J=8.1 Hz, 1H), 7.87 (d, J=8.4 Hz, 2H), 7.97 (d, J=7.8 Hz, 1H), 8.07 (s, 1H). MS m/z: 519 (M+1)

후처리

  1. customThe organic layer was separated
  2. washthe aqueous layer was washed with an addition portion of dichloromethane (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-5c21f22e28494da3ba8e3fa18158ad97
출처 데이터셋
uspto-grants-2011_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08067415B2

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