1-Pyrrolidineethanamine → Ammonia

HRID 1866546Notes

Reaction equation

HRID 1866546 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]1[CH2:8][CH2:7][CH2:6][CH2:5]1.Cl.CN(C)CCCN=C=NCC.[Si:21]([O:28][C@H:29]([C:45]1[CH:50]=[CH:49][C:48]([OH:51])=[C:47]([CH2:52][OH:53])[CH:46]=1)[CH2:30][NH:31][C:32]([CH3:44])([CH3:43])[CH2:33][C:34]1[CH:35]=[C:36]([CH:40]=[CH:41][CH:42]=1)[C:37](O)=[O:38])([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22].O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[NH3:1].[Si:21]([O:28][C@H:29]([C:45]1[CH:50]=[CH:49][C:48]([OH:51])=[C:47]([CH2:52][OH:53])[CH:46]=1)[CH2:30][NH:31][C:32]([CH3:44])([CH3:43])[CH2:33][C:34]1[CH:35]=[C:36]([CH:40]=[CH:41][CH:42]=1)[C:37]([NH:1][CH2:2][CH2:3][N:4]1[CH2:8][CH2:7][CH2:6][CH2:5]1)=[O:38])([C:24]([CH3:25])([CH3:26])[CH3:27])([CH3:23])[CH3:22]

Participants

8

Reactant 5

HCID 13441-PyrrolidineethanamineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 579783093-{2-[(2R)-2-(tert-butyldimethyl silanyloxy)-2-(4-hydroxy-3-hydroxymethyl-phenyl)ethylamino]-2-methylpropyl}benzoic acid

Product 2

HCID 222AmmoniaHCID 690248053-[2-({(2R)-2-{[tert-Butyl(dimethyl)silyl]oxy}-2-[4-hydroxy-3-(hydroxyl methyl)phenyl]ethyl}amino)-2-methylpropyl]-N-(2-pyrrolidin-1-ylethyl)benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(2-Aminoethyl)pyrrolidine (83 μL, 0.63 mmol) was added to a mixture of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (122 mg, 0.63 mmol), 3-{2-[(2R)-2-(tert-butyldimethylsilanyloxy)-2-(4-hydroxy-3-hydroxy methyl-phenyl)ethylamino]-2-methylpropyl}benzoic acid (preparation 37) (200 mg, 0.42 mmol), 1-hydroxybenzotriazole hydrate (63 mg, 0.47 mmol) and N,N-diisopropylethylamine (88 □L, 0.63 mmol) in N,N-dimethylformamide (5 mL). The resulting solution was stirred for 18 hours at room temperature. The solvent was removed in vacuo and the residue was partitioned between ethyl acetate (50 mL) and saturated sodium hydrogen carbonate solution (10 mL). The aqueous layer was separated and re-extracted with dichloromethane (30 mL), and the combined organic solution was dried (sodium sulfate) and concentrated in vacuo to give a yellow oil. The oil was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:0.88 ammonia, 100:0:0 to 75:25:2 to afford the title compound as a pale yellow solid. 1H NMR (400 MHz, CD3OD) δ: 7.69 (2H, m) 7.40-7.31 (2H, m), 7.26 (1H, m), 7.14-7.03 (1H, dd), 6.85 (1H, d), 4.69 (1H, m), 4.62 (2H, m), 3.58 (2H, m), 2.89-2.59 (10H, m), 1.82-1.79 (4H, m), 1.12 (3H, s), 1.07 (3H, s), 0.79 (9H, s), −0.01 (3H, s), −0.21 (3H, s) ppm; LRMS APCI m/z 570 [M+H]+

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was partitioned between ethyl acetate (50 mL) and saturated sodium hydrogen carbonate solution (10 mL)
  3. customThe aqueous layer was separated
  4. extractionre-extracted with dichloromethane (30 mL)
  5. dry with materialthe combined organic solution was dried (sodium sulfate)
  6. concentrationconcentrated in vacuo
  7. customto give a yellow oil
  8. customThe oil was purified by flash column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-9cee1c98210948a98d44f06226f91ebe
Source dataset
uspto-grants-2009_12
Patent number
US07629358B2

Reaction notes

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