Water → HCID 67254404, compound

HRID 2042130Notes

Reaction equation

HRID 2042130 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23]([CH2:27][O:28][Si](C(C)(C)C)(C)C)[CH:22]=3)=[CH:16][C:15]=2[F:36])=[O:12])[N:7]([C:37]2[CH:38]=[C:39]3[C:44](=[CH:45][CH:46]=2)[N:43]=[CH:42][CH:41]=[CH:40]3)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-].O>C1COCC1>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[CH:26]=[CH:25][N:24]=[C:23]([CH2:27][OH:28])[CH:22]=3)=[CH:16][C:15]=2[F:36])=[O:12])[N:7]([C:37]2[CH:38]=[C:39]3[C:44](=[CH:45][CH:46]=2)[N:43]=[CH:42][CH:41]=[CH:40]3)[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 962WaterHCID 2724141Tetrabutylammonium FluorideHCID 67252302HCID 67252302, compound

Product 1

HCID 67254404HCID 67254404, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-(3-tert-butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl)-3-(4-(2-((tert-butyldimethylsilyloxy)methyl)pyridin-4-yloxy)-2-fluorophenyl)urea (0.12 g, 0.19 mmol) in THF (2 ml) was treated with TBAF (1.0 ml, 1.0 M solution in THF) at RT for 1 hour. Water (10 ml) was added and the separated solid was filtered, washed with water and dried to give desilylated product 1-(3-tert-butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl)-3-(2-fluoro-4-(2-(hydroxymethyl)pyridin-4-yloxy)phenyl)urea as a white solid (0.090 g, 91% yield). 1H NMR (400 MHz, DMSO-d6) δ 9.01 (brs, 1H), 8.97 (dd, J=4.2, 1.6 Hz, 2H), 8.50 (brd, J=8.3 Hz, 1H), 8.36 (d, J=5.5 Hz, 2H), 8.18 (m, 2H), 7.97 (dd, J=9, 2 Hz, 1H), 7.63 (dd, J=9, 4.4 Hz, 1H), 7.22 (dd, J=12, 2.5 Hz, 1H), 6.99 (m, 1H), 6.93 (d, J=2.5 Hz, 1H), 6.82 (dd, J=5.7, 2.5 Hz, 1H), 6.48 (s, 1H), 5.40 (t, J=6 Hz, 1H), 4.50 (d, J=8 Hz, 2H), 1.32 (s, 9H); MS (ESI) m/z: 527.2 (M+H+). The free base was converted to hydrochloride salt. 1H NMR (400 MHz, DMSO-d6) δ 9.31 (brs, 1H), 9.23 (m, 1H), 9.07 (dd, J=4.2, 1.6 Hz, 1H), 8.70 (brd, J=8.3 Hz, 1H), 8.65 (d, J=6.8 Hz, 2H), 8.32 (d, J=2 Hz, 1H), 8.27 (d, J=9 Hz, 1H), 8.22 (d, J=9 Hz, 1H), 8.09 (dd, J=9, 2.3 Hz, 1H), 7.75 (dd, J=8, 4.5 Hz, 1H), 7.43-7.37 (m, 2H), 7.34 (d, 2.8 Hz, 1H), 7.12 (m, 1H), 6.48 (s, 1H), 4.77 (s, 2H), 1.32 (s, 9H); MS (ESI) m/z: 527.2 (M+H+).

Workup

  1. filtrationthe separated solid was filtered
  2. washwashed with water
  3. customdried
  4. customto give

Sources & evidence

ORD record
ord-bf31e3108653499dbf6a58ab7b1ce9c1
Source dataset
uspto-grants-2013_11
Patent number
US08586565B2

Reaction notes

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