1-Butanol → 2-[(2S)-2-(6-chloro-3-oxo-1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-3-cyclohexylpropyl]-1H-isoindole-1,3(2H)-dione

HRID 340007Notes

Reaction equation

HRID 340007 reaction equation
Br[CH2:2][C:3]1[C:8]([C:9]([O:11]C)=O)=[CH:7][N:6]=[C:5]([Cl:13])[CH:4]=1.Cl.[NH2:15][C@@H:16]([CH2:29][CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)[CH2:17][N:18]1[C:26](=[O:27])[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]1=[O:28].C(N(CC)C(C)C)(C)C.C(O)CCC>>[Cl:13][C:5]1[N:6]=[CH:7][C:8]2[C:9](=[O:11])[N:15]([C@@H:16]([CH2:29][CH:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)[CH2:17][N:18]3[C:19](=[O:28])[C:20]4[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:26]3=[O:27])[CH2:2][C:3]=2[CH:4]=1

Participants

5

Reactant 4

HCID 2631-ButanolHCID 81531DiisopropylethylamineHCID 86681474Methyl 4-(bromomethyl)-6-chloronicotinateHCID 866814942-[(2S)-2-amino-3-cyclohexylpropyl]-1H-isoindole-1,3(2H)-dione hydrochloride

Product 1

HCID 866814932-[(2S)-2-(6-chloro-3-oxo-1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-3-cyclohexylpropyl]-1H-isoindole-1,3(2H)-dioneYield 55.1%

Conditions

Temperature
140 °C

Procedure

A mixture of methyl 4-(bromomethyl)-6-chloronicotinate (200.0 mg, 0.7561 mmol) (prepared according to Example 119, Steps A, B and C), 2-[(2S)-2-amino-3-cyclohexylpropyl]-1H-isoindole-1,3(2H)-dione hydrochloride (244 mg, 0.754 mmol) (prepared from Example 79, Step A) and N,N-diisopropylethylamine (0.526 mL, 3.02 mmol) in 1-butanol (5.0 mL, 55 mmol) was stirred at 140° C. for 2 h under microwave irradiation. Direct purification on prep.HPLC afforded 182 mg (55.1% yield) of the desired product. LC-MS found: 438.1 (M+H)+.

Workup

  1. customDirect purification

Sources & evidence

ORD record
ord-9f42dd42e7594830914df599dddfbb6f
Source dataset
uspto-grants-2014_11
Patent number
US08895571B2

Reaction notes

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