Hydrochloric Acid → Tetrahydro-pyran-4-carboxylic acid [2-methyl-6-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-yl]-amide

HRID 536310Notes

Reaction equation

HRID 536310 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.[O:20]1[CH2:25][CH2:24][CH:23]([C:26](O)=[O:27])[CH2:22][CH2:21]1.CN1CCOCC1.ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.Cl.Cl>C(Cl)Cl.CN(C=O)C>[CH3:1][C:2]1[C:7]([NH:8][C:26]([CH:23]2[CH2:24][CH2:25][O:20][CH2:21][CH2:22]2)=[O:27])=[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

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 219302Oxane-4-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 674803792-Methyl-6-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-yl-amine

Product 1

HCID 68212926Tetrahydro-pyran-4-carboxylic acid [2-methyl-6-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-yl]-amideYield 73%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-methyl-6-((2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-3-yl amine (0.1 g, 0.385 mmol) in DCM (3 mL) and DMF (1 mL), was added sequentially tetrahydro-2H-pyran-4-carboxlic acid (0.06 g, 0.461 mmol), N-methylmorpholine (0.127 mL, 1.16 mmol), 1-hydroxylbenzotriazole (HOBT) (0.068 g, 0.504 mmol), and EDCl.HCl (0.096 g, 0.504 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 0.103 g (73%) 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-637c37adcbad4c8fb56974594acbd538
Source dataset
uspto-grants-2014_10
Patent number
US08859588B2

Reaction notes

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