Hydrochloric Acid → N-{[5-hydroxy-6-(1-methylethyl)-2-({3-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]phenyl}methyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine

HRID 2046297ノート

反応式

HRID 2046297 の反応式
Br[C:2]1[CH:3]=[C:4]([CH2:8][N:9]2[C:14](=[O:15])[C:13]([C:16]([NH:18][CH2:19][C:20]([OH:22])=[O:21])=[O:17])=[C:12]([OH:23])[C:11]([CH:24]([CH3:26])[CH3:25])=[N:10]2)[CH:5]=[CH:6][CH:7]=1.[CH3:27][N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:39]=[CH:38][C:37](B3OC(C)(C)C(C)(C)O3)=[CH:36][N:35]=2)[CH2:30][CH2:29]1.C(=O)([O-])[O-].[K+].[K+].Cl>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:23][C:12]1[C:11]([CH:24]([CH3:26])[CH3:25])=[N:10][N:9]([CH2:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([C:37]3[CH:36]=[N:35][C:34]([N:31]4[CH2:30][CH2:29][N:28]([CH3:27])[CH2:33][CH2:32]4)=[CH:39][CH:38]=3)[CH:3]=2)[C:14](=[O:15])[C:13]=1[C:16]([NH:18][CH2:19][C:20]([OH:22])=[O:21])=[O:17]

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 27696181-Methyl-4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazineHCID 54739211N-{[2-[(3-Bromophenyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine

生成物 1

HCID 54739190N-{[5-hydroxy-6-(1-methylethyl)-2-({3-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]phenyl}methyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine収率 65.8%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒2 回HCID 312751,4-Dioxane溶媒

実験手順

To a 5 mL microwave tube was added N-{[2-[(3-bromophenyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine (example 79, 31 mg, 0.073 mmol), 1-methyl-4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl]piperazine (22.16 mg, 0.073 mmol), potassium carbonate (303 mg, 2.192 mmol), and tetrakis(triphenylphosphine)palladium (0) (2.53 mg, 2.192 μmol) in 1,4-Dioxane (1.5 ml) and Water (0.500 ml). The mixture was irradiated at 100° C. for 20 minutes. The reaction mixture was diluted with water (4 ml) and acidified with 1N HCl (1 ml) then filtered to remove any residue followed by purification by HPLC chromatography (ODS silica, gradient 10-75% acetonitrile/water (0.1% TFA)) to afford the title compound N-{[5-hydroxy-6-(1 -methylethyl)-2-({3-[6-(4-methyl-1-piperazinyl)-3-pyridinyl]phenyl}methyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycine (32 mg, 0.048 mmol, 65.7% yield) as a white powder. 1H NMR (400 MHz, DMSO-d6) d ppm 15.88 (s, 1H), 12.98 (br. s., 1H), 10.18 (t, J=5.56 Hz, 1 H), 9.71 (br. s., 1H), 8.46 (d, J=2.27 Hz, 1H), 7.91 (dd, J=8.84, 2.53 Hz, 1H), 7.52-7.61 (m, 2H), 7.42 (t, J=8.08 Hz, 1H), 7.23 (d, J=7.58 Hz, 1H), 7.07 (d, J=9.09 Hz, 1H), 5.32 (s, 2H), 4.48 (d, J=12.63 Hz, 2H), 4.09 (d, J=5.56 Hz, 2H), 3.52 (d, J=10.36 Hz, 2H), 3.00-3.26 (m, 5H), 2.86 (d, J=4.04 Hz, 3H), 1.21 (d, J=6.82 Hz, 6H). MS (ES+) m/e 521 [M+H]+.

後処理

  1. customThe mixture was irradiated at 100° C. for 20 minutes
  2. filtrationthen filtered
  3. customto remove any residue
  4. customfollowed by purification by HPLC chromatography (ODS silica, gradient 10-75% acetonitrile/water (0.1% TFA))

出典と根拠

ORDレコード
ord-6d64b234d6be4f9ea85193ee337839b4
出典データセット
uspto-grants-2013_11
特許番号
USRE044613E1

反応ノート

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