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

HRID 2401130노트

반응식

HRID 2401130 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+]>ClC(Cl)C.ClCCl>[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 674803792-Methyl-6-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-yl-amine

생성물 1

HCID 712804254-{2-[2-Methyl-6-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-ylamino]-ethyl}-tetrahydro-pyran-4-carboxylic acid methyl ester수율 35%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 63651,1-Dichloroethane용매2회

실험 절차

To a solution of 2-methyl-6-((2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-3-ylamine (0.075 g, 0.288 mmol) in 1-2 dichloroethane (DCE, 6 mL) was added a solution of 4-(2-oxo-ethyl)-tetrahydro-pyran-4-carboxylic acid methyl ester (0.053 g, 0.288 mmol) in DCE (2 mL), acetic acid (3.1 eq) and allowed to stir at room temperature for an hour. NaBH(OAc)3 (3 eq.) was then added in one portion and reaction mixture was allowed to stir at room temperature for 16 hours. The reaction mixture was diluted with dichloromethane (DCM, 5.0 mL), quenched with 2 M of NH4OH in water. Aqueous layer was extracted with DCM (5.0 mL×2). Combined organics were washed with aqueous NaHCO3 (15 mL), brine (30 mL), and dried over Na2SO4, and concentrated under vacuum. Purification by column chromatography on silica gel eluting with methanol in dichloromethane (0-10%) afforded 0.04 g (35%) of the title compound.

후처리

  1. stirringto stir at room temperature for 16 hours
  2. customquenched with 2 M of NH4OH in water
  3. extractionAqueous layer was extracted with DCM (5.0 mL×2)
  4. washCombined organics were washed with aqueous NaHCO3 (15 mL), brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under vacuum
  7. customPurification by column chromatography on silica gel eluting with methanol in dichloromethane (0-10%)

출처 및 근거

ORD 기록
ord-41e2553d0df34372a485cbc2bee717d6
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08796278B2

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