Diisopropylethylamine → (S)-N-(4-(1-(2-methylbutanoyl)azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide

HRID 929888Notes

Reaction equation

HRID 929888 reaction equation
[NH:1]1[CH2:4][CH:3]([O:5][C:6]2[CH:11]=[CH:10][C:9]([NH:12][C:13]([N:15]3[CH2:18][CH:17]([C:19]4[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=4)[CH2:16]3)=[O:14])=[CH:8][CH:7]=2)[CH2:2]1.[CH3:25][C@@H:26]([CH2:30][CH3:31])[C:27](O)=[O:28].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C)C=O.ClCCl.O>[CH3:25][C@@H:26]([CH2:30][CH3:31])[C:27]([N:1]1[CH2:2][CH:3]([O:5][C:6]2[CH:11]=[CH:10][C:9]([NH:12][C:13]([N:15]3[CH2:18][CH:17]([C:19]4[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=4)[CH2:16]3)=[O:14])=[CH:8][CH:7]=2)[CH2:4]1)=[O:28]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 448893(S)-2-methylbutanoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 90010911N-(4-(azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide

Product 1

HCID 72202677(S)-N-(4-(1-(2-methylbutanoyl)azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

N-(4-(azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide (1 g, 1.805 mmol), (S)-2-methylbutanoic acid (0.221 g, 2.166 mmol), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.519 g, 2.71 mmol) were combined in in dimethylformamide (9.03 mL) at room temperature. 1-Hydroxybenzotriazole hydrate (0.415 g, 2.71 mmol) and diisopropylethylamine (0.946 ml, 5.42 mmol) were added and the reaction mixture was stirred overnight at room temperature. Water and dichloromethane were added and the organics were removed by pipet. Concentration and reverse phase chromatography gave (S)—N-(4-(1-(2-methylbutanoyl)azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide. 1H NMR (300 MHz, DMSO-d6) δ 8.56 (d, J=2.4 Hz, 1H), 8.48 (dd, J=4.7, 1.6 Hz, 1H), 8.41 (s, 1H), 7.86 (dt, J=7.9, 2.0 Hz, 1H), 7.46-7.37 (m, 3H), 6.76 (d, J=8.9 Hz, 2H), 4.96 (dd, J=6.3, 3.4 Hz, 1H), 4.62-4.53 (m, 1H), 4.36 (d, J=15.9 Hz, 2H), 4.32-4.22 (m, 1H), 4.11-4.02 (m, 1H), 3.98-3.81 (m, 3H), 3.75 (dd, J=10.6, 3.9 Hz, 1H), 2.36-2.20 (m, 1H), 1.59-1.39 (m, 1H), 1.38-1.20 (m, 1H), 0.96 (dd, J=6.8, 3.9 Hz, 3H), 0.82 (q, J=7.2 Hz, 3H); MS (ESI(+)) m/e 409 (M+H)11.

Workup

  1. customthe organics were removed by pipet
  2. concentrationConcentration

Sources & evidence

ORD record
ord-639abc7c503142638e23f14f431eb960
Source dataset
uspto-grants-2016_03
Patent number
US09296723B2

Reaction notes

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