Diisopropylethylamine → N-(3-tert-butyl-1-{3-[[(dimethylamino)sulfonyl](3-hydroxypropyl)amino]phenyl}-1H-pyrazol-5-yl)-N'-[4-(pyridin-4-yloxy)phenyl]urea

HRID 221900Notes

Reaction equation

[C:1]([C:5]1[CH:6]=[C:7]([NH:21][C:22]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][C:32]3[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=3)=[CH:27][CH:26]=2)=[O:23])[N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([NH:16][CH2:17][CH2:18][CH2:19][OH:20])[CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:38][N:39]([CH3:44])[S:40](Cl)(=[O:42])=[O:41].CCN(C(C)C)C(C)C>C1COCC1>[C:1]([C:5]1[CH:6]=[C:7]([NH:21][C:22]([NH:24][C:25]2[CH:26]=[CH:27][C:28]([O:31][C:32]3[CH:33]=[CH:34][N:35]=[CH:36][CH:37]=3)=[CH:29][CH:30]=2)=[O:23])[N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([N:16]([S:40]([N:39]([CH3:44])[CH3:38])(=[O:42])=[O:41])[CH2:17][CH2:18][CH2:19][OH:20])[CH:11]=2)[N:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 40 °C

Procedure

A solution of 1-{5-tert-butyl-2-[3-(3-hydroxy-propylamino)-phenyl]-2H-pyrazol-3-yl}-3-[4-(pyridin-4-yloxy)-phenyl]-urea (100 mg, 0.21 mmol) in THF (1 mL) was treated with dimethylsulfamoyl chloride (90 mg, 0.62 mmol, 3 eq) followed by DIEA (30 mg, 0.21 mmol, 1 eq). The reaction mixture was stirred at 40° C. overnight. The mixture was evaporated at reduced pressure, and the product was isolated by MPLC (eluting with 1% to 4% MeOH in DCM) to afford 57 mg (46%) of desired product. 1H-NMR (DMSO-d6) δ 9.08 (s, 1H), 8.40-8.38 (m, 3H), 7.54-7.36 (m, 6H), 7.05 (d, J=8.9 Hz, 2H), 6.84 (d, J=5.6 Hz, 2H), 6.32 (s, 1H), 4.45 (t, J=4.6 Hz, 1H), 3.64 (t, J=7.0 Hz, 2H), 3.33-3.28 (m, 2H), 2.70 (s, 6H), 1.49-1.45 (m, 2H), 1.29 (s, 9H); MS LC-MS [M+H]+=608.2, RT=2.45 min.

Workup

customThe mixture was evaporated at reduced pressure
customthe product was isolated by MPLC (eluting with 1% to 4% MeOH in DCM)

Sources & evidence

ORD record: ord-8aa5f68cf3fe40eabfbe4a10063c7adf
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08207166B2

Reaction notes

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