Acetic Acid → 4-{2-[2-Methyl-6-((2S,3'R)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-ylamino]-ethyl}-tetrahydro-pyran-4-carboxylic acid methyl ester

HRID 2401117

반응식

HRID 2401117 반응식
[CH3:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[C:4]([N:9]2[CH2:13][CH2:12][C@@H:11]([N:14]3[CH2:18][CH2:17][CH2:16][C@@H:15]3[CH3:19])[CH2:10]2)[N:3]=1.[CH3:20][O:21][C:22]([C:24]1([CH2:30][CH:31]=O)[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1)=[O:23].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[CH3:20][O:21][C:22]([C:24]1([CH2:30][CH2:31][NH:8][C:7]2[C:2]([CH3:1])=[N:3][C:4]([N:9]3[CH2:13][CH2:12][C@@H:11]([N:14]4[CH2:18][CH2:17][CH2:16][C@@H:15]4[CH3:19])[CH2:10]3)=[CH:5][CH:6]=2)[CH2:25][CH2:26][O:27][CH2:28][CH2:29]1)=[O:23]

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 58468045methyl 4-(2-oxoethyl)tetrahydro-2H-pyran-4-carboxylateHCID 674804612-methyl-6-[(3R)-3-[(2S)-2-methylpyrrolidin-1-yl]pyrrolidin-1-yl]pyridin-3-amine

생성물 1

HCID 712803374-{2-[2-Methyl-6-((2S,3'R)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-ylamino]-ethyl}-tetrahydro-pyran-4-carboxylic acid methyl ester수율 97.1%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매2회HCID 6344Dichloromethane용매

실험 절차

2-Methyl-6-((2S,3′R)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-3-ylamine (58 mg, 0.22 mmol) was dissolved in DCE (1 mL). To this solution was transferred a solution of 4-(2-oxo-ethyl)tetrahydro-pyran-4-carboxylic acid methyl ester (40 mg, 0.22 mmol) in DCE (1 mL). To this clear solution was then added acetic acid (38 μL, 0.66 mmol), followed by addition of powdered NaBH(OAc)3 (140 mg, 0.66 mmol) in one portion under N2 at rt. The yellowish milky solution was stirred at rt. overnight. The reaction was diluted with DCM (40 mL) and quenched with 30 mL of concentrated NH4OH in 70 mL of water. The two layers were separated, and the aqueous layer was extracted with DCM (10 mL×2). The combined DCM extracts were washed with sodium bicarbonate (10 mL), and brine (15 mL), dried (anhydrous potassium carbonate), filtered, and concentrated obtain 92 mg of a crude solid, which was used in the next step of the reaction without purification.

후처리

  1. customovernight
  2. customquenched with 30 mL of concentrated NH4OH in 70 mL of water
  3. customThe two layers were separated
  4. extractionthe aqueous layer was extracted with DCM (10 mL×2)
  5. washThe combined DCM extracts were washed with sodium bicarbonate (10 mL), and brine (15 mL)
  6. dry with materialdried (anhydrous potassium carbonate)
  7. filtrationfiltered
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-1a2e81ffc99940c6853a71502780ab95
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08796278B2

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