O-(tert-Butyldimethylsilyl)hydroxylamine → N-hydroxy-4-(4-(4-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)thiazol-2-yl)tetrahydropyran-4-yl)benzamide

HRID 415949

Reaction equation

HRID 415949 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[N:13]=[CH:12][C:11]([C:14]3[N:15]=[C:16]([C:19]4([C:25]5[CH:33]=[CH:32][C:28]([C:29]([OH:31])=O)=[CH:27][CH:26]=5)[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)[S:17][CH:18]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.CN(C([O:41][N:42]1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.NO[Si](C(C)(C)C)(C)C>CN(C=O)C>[OH:41][NH:42][C:29](=[O:31])[C:28]1[CH:27]=[CH:26][C:25]([C:19]2([C:16]3[S:17][CH:18]=[C:14]([C:11]4[CH:12]=[N:13][C:8]([N:5]5[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]5)=[CH:9][CH:10]=4)[N:15]=3)[CH2:20][CH2:21][O:22][CH2:23][CH2:24]2)=[CH:33][CH:32]=1

Participants

5

Reactant 3

HCID 4691350O-(tert-Butyldimethylsilyl)hydroxylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 666195274-(4-{4-[6-(4-Methyl-piperazin-1-yl)-pyridin-3-yl]-thiazol-2-yl}-tetrahydro-pyran-4-yl)-benzoic acid

Product 1

HCID 59160866N-hydroxy-4-(4-(4-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)thiazol-2-yl)tetrahydropyran-4-yl)benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-(4-{4-[6-(4-methyl-piperazin-1-yl)-pyridin-3-yl]-thiazol-2-yl}-tetrahydro-pyran-4-yl)-benzoic acid (200 mg, 0.215 mmol), HATU (90 mg, 1.1 eq), H2N-OTBS (2.0 eq), and TEA (0.1 mL, 3 eq) were mixed in DMF and stirred for 2 hours. The reaction mixture was washed with water and then extracted with EtOAc. The organic phase was evaporated, suspended in 1N HCl, and slowly evaporated at 50° C. for 30 minutes to give title compound. MS found for C25H29N5O3S as (M+H)+ 480.15. 1H NMR (400 MHz, dmso-d6): δ: 11.13 (s, 1H), 8.99 (s, 1H), 8.68 (d, J=2.4 Hz, 1H), 8.00 (dd, J=8.8, 6.4 Hz, 1H), 7.81 (s, 1H), 7.68 (d, J=8.4 Hz, 2H), 7.50 (d, J=8.4 Hz, 2H), 6.87 (d, J=8.8 Hz, 1H), 3.73-3.70 (m, 2H), 3.61-3.56 (m, 2H), 3.53-3.50 (m, 4H), 2.65-2.60 (m, 2H), 2.44-2.20 (m, 4H), 2.38-2.32 (m, 2H), 2.22 (s, 3H).

Workup

  1. washThe reaction mixture was washed with water
  2. extractionextracted with EtOAc
  3. customThe organic phase was evaporated
  4. customslowly evaporated at 50° C. for 30 minutes

Sources & evidence

ORD record
ord-b5469fe783d4478a91099c257d5c9ddd
Source dataset
uspto-grants-2012_01
Patent number
US08088771B2

Linked notes

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