(-)-2-Butanol → [(1R)-1-Methylpropyl]1-[8-methoxy-5-(1-oxo-3H-isobenzofuran-5-yl)-[1,2,4]triazolo-[1,5-a]pyridin-2-yl]cyclopropanecarboxylate

HRID 710938

Reaction equation

HRID 710938 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[N:5]([N:19]=[C:20]([C:22]3([C:25]([OH:27])=[O:26])[CH2:24][CH2:23]3)[N:21]=2)[C:6]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[C:14](=[O:18])[O:13][CH2:12]3)=[CH:7][CH:8]=1.[CH3:28][C@@H:29](O)[CH2:30][CH3:31].CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:28][C@@H:29]([O:26][C:25]([C:22]1([C:20]2[N:21]=[C:4]3[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[C:6]([C:9]4[CH:10]=[C:11]5[C:15](=[CH:16][CH:17]=4)[C:14](=[O:18])[O:13][CH2:12]5)[N:5]3[N:19]=2)[CH2:23][CH2:24]1)=[O:27])[CH2:30][CH3:31]

Participants

6

Reactant 3

HCID 84682(-)-2-ButanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 686549441-[5-(1,3-dihydro-1-oxo-5-isobenzofuranyl)-8-methoxy[1,2,4]triazolo[1,5-a]pyridin-2-yl]Cyclopropanecarboxylic acid

Product 1

HCID 71611997[(1R)-1-Methylpropyl]1-[8-methoxy-5-(1-oxo-3H-isobenzofuran-5-yl)-[1,2,4]triazolo-[1,5-a]pyridin-2-yl]cyclopropanecarboxylateYield 30%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-[8-methoxy-5-(1-oxo-3H-isobenzofuran-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxylic acid (400 mg, 1.095 mmol), (2R)-butan-2-ol (122 mg, 1.64 mmol), DMAP (147 mg, 1.20 mmol) and EDCI.HCl (231 mg, 1.20 mmol) in DCM (10 mL) was stirred at RT overnight before it was evaporated to dryness. Column chromatography (gradient MeOH 0 to 5% in DCM) followed by recrystallization in EtOH and freeze drying afforded the title compound as colorless powder (138 mg, 30%). HPLC-Retention time (XE Metode 7 CM): 2.33 minutes. Detected “M+1”-mass: 422.15. Calculated “M+1”-mass: 422.17. 1H NMR (DMSO, 400 MHz): δ=8.23 (br s, 1H), 8.14 (dd, 1H, J=8.0, 1.6 Hz), 7.99 (d, 1H, J=8.0 Hz), 7.41 (d, 1H, J=8.2 Hz), 7.24 (d, 1H, J=8.2 Hz), 5.51 (s, 2H), 4.78 (h, 1H, J=6.3 Hz), 4.04 (s, 3H), 1.62-1.38 (m, 6H), 1.13 (d, 3H, J=6.3 Hz), 0.78 (t, 3H, J=7.4 Hz) ppm.

Workup

  1. customwas evaporated to dryness
  2. customColumn chromatography (gradient MeOH 0 to 5% in DCM) followed by recrystallization in EtOH
  3. customfreeze drying

Sources & evidence

ORD record
ord-9d547536270b447e93c7ede56c5b6b27
Source dataset
uspto-grants-2015_11
Patent number
US09181248B2

Linked notes

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