Hydrochloric Acid → Tetrahydro-pyran-4-carboxylic acid [5-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-2-yl]-amide

HRID 536311Notes

Reaction equation

HRID 536311 reaction equation
[CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C@H:7]1[CH2:11][CH2:10][N:9]([C:12]2[CH:13]=[CH:14][C:15]([NH2:18])=[N:16][CH:17]=2)[CH2:8]1.[O:19]1[CH2:24][CH2:23][CH:22]([C:25](O)=[O:26])[CH2:21][CH2:20]1.CN1CCOCC1.ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.Cl.Cl>C(Cl)Cl.CN(C=O)C>[CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C@H:7]1[CH2:11][CH2:10][N:9]([C:12]2[CH:13]=[CH:14][C:15]([NH:18][C:25]([CH:22]3[CH2:23][CH2:24][O:19][CH2:20][CH2:21]3)=[O:26])=[N:16][CH:17]=2)[CH2:8]1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 219302Oxane-4-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68211102HCID 68211102, compound

Product 1

HCID 54597008Tetrahydro-pyran-4-carboxylic acid [5-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-2-yl]-amideYield 4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-((2S,3′S)-2-Methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-2-ylamine (0.091 g, 0.369 mmol) in DCM (3 mL) and DMF (1 mL), was added sequentially tetrahydro-2H-pyran-4-carboxlic acid (0.058 g, 0.443 mmol), N-methylmorpholine (0.122 mL, 1.11 mmol), 1-hydroxylbenzotriazole (HOBT) (0.065 g, 0.481 mmol), and EDCl.HCl (0.092 g, 0.481 mmol). The reaction mixture was stirred at room temperature for 16 hours. The reaction was quenched with a saturated aqueous solution of sodium bicarbonate (3 mL) and 15 mL of dichloromethane. The aqueous layer was extracted with dichloromethane (15 mL, 2×). The combined organic layers were washed with sodium bicarbonate (15 mL), brine (15 mL), dried over Na2SO4, and concentrated under vacuum. Purification by column chromatography on silica gel (0-10%) methanol in dichloromethane afforded 4.7 mg (4.0%) of the title compound.

Workup

  1. customThe reaction was quenched with a saturated aqueous solution of sodium bicarbonate (3 mL) and 15 mL of dichloromethane
  2. extractionThe aqueous layer was extracted with dichloromethane (15 mL, 2×)
  3. washThe combined organic layers were washed with sodium bicarbonate (15 mL), brine (15 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under vacuum
  6. customPurification by column chromatography on silica gel (0-10%) methanol in dichloromethane

Sources & evidence

ORD record
ord-c3852531ab604d749b612b72268fd716
Source dataset
uspto-grants-2014_10
Patent number
US08859588B2

Reaction notes

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