Diisopropylethylamine → HCID 70980146, compound

HRID 81982Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:14]3[C:15]([CH3:20])=[N:16][O:17][C:18]=3[CH3:19])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:21]([NH2:23])=[O:22].CCN(C(C)C)C(C)C.[O:33]1[CH2:38][CH2:37][CH:36]([CH2:39][NH2:40])[CH2:35][CH2:34]1>CN1C(=O)CCC1>[CH3:20][C:15]1[C:14]([C:8]2[CH:7]=[C:6]3[C:11]([C:2]([NH:40][CH2:39][CH:36]4[CH2:37][CH2:38][O:33][CH2:34][CH2:35]4)=[C:3]([C:21]([NH2:23])=[O:22])[CH:4]=[N:5]3)=[CH:10][C:9]=2[O:12][CH3:13])=[C:18]([CH3:19])[O:17][N:16]=1

Participants

Conditions

Temperature: 120 °C

Procedure

4-Chloro-7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-3-quinolinecarboxamide (for a preparation see Intermediate 9) (1.890 g, 5.70 mmol) was dissolved in NMP (5 ml), DIPEA (2.487 ml, 14.24 mmol) was added followed by (tetrahydro-2H-pyran-4-yl)methanamine (0.82 g, 7.12 mmol) and the mixture was heated at 120° C. for 3 h, then cooled and the brown solution loaded onto a 70 g SCX-2 cartridge, the column washed with methanol (200 ml) and then eluted with 2M methanolic ammonia (100 ml) and methanol (100 ml). The eluant was evaporated in vacuo to give a brown solid. This was triturated with EtOAc (30 ml) and the solid collected by filtration to give 7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]-3-quinolinecarboxamide (1.58 g, 3.85 mmol, 54.1% yield) as brown solid. LCMS (formate) Rt 0.64, MH+ 411

Workup

temperaturecooled
washthe column washed with methanol (200 ml)
washeluted with 2M methanolic ammonia (100 ml) and methanol (100 ml)
customThe eluant was evaporated in vacuo
customto give a brown solid
customThis was triturated with EtOAc (30 ml)
filtrationthe solid collected by filtration

Sources & evidence

ORD record: ord-9b0cf772885b4d9a8e976d4aded97ba8
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846709B2

Reaction notes

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