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 2401130Notes

Reaction equation

HRID 2401130 reaction equation
[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]

Participants

7

Reactant 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

Product 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 esterYield 35%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent2×

Procedure

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.

Workup

  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%)

Sources & evidence

ORD record
ord-41e2553d0df34372a485cbc2bee717d6
Source dataset
uspto-grants-2014_08
Patent number
US08796278B2

Reaction notes

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