Sodium Carbonate → 2-(6-(benzo[c][1,2,5]thiadiazol-5-ylamino)-4-(isopropylamino)pyridin-3-yl)-N-(3-hydroxypropyl)-5-methyloxazole-4-carboxamide

HRID 595414ノート

反応式

HRID 595414 の反応式
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:20])=[C:11]([C:13]([NH:15][CH2:16][CH2:17][CH2:18][OH:19])=[O:14])[N:12]=2)=[C:4]([NH:21][CH:22]([CH3:24])[CH3:23])[CH:3]=1.[N:25]1[S:26][N:27]=[C:28]2[CH:33]=[C:32]([NH2:34])[CH:31]=[CH:30][C:29]=12.C([O-])([O-])=O.[Na+].[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:25]1[S:26][N:27]=[C:28]2[CH:33]=[C:32]([NH:34][C:2]3[N:7]=[CH:6][C:5]([C:8]4[O:9][C:10]([CH3:20])=[C:11]([C:13]([NH:15][CH2:16][CH2:17][CH2:18][OH:19])=[O:14])[N:12]=4)=[C:4]([NH:21][CH:22]([CH3:24])[CH3:23])[CH:3]=3)[CH:31]=[CH:30][C:29]=12

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 3143132,1,3-Benzothiadiazol-5-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 896896522-(6-chloro-4-(isopropylamino)pyridin-3-yl)-N-(3-hydroxypropyl)-5-methyloxazole-4-carboxamide

生成物 1

HCID 896897652-(6-(benzo[c][1,2,5]thiadiazol-5-ylamino)-4-(isopropylamino)pyridin-3-yl)-N-(3-hydroxypropyl)-5-methyloxazole-4-carboxamide

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
115 °C

実験手順

To a stirred solution of (2-(6-chloro-4-(isopropylamino)pyridin-3-yl)-N-(3-hydroxypropyl)-5-methyloxazole-4-carboxamide (31) (100 mg, 0.283 mmol) in 1,4-Dioxane (10 mL), benzo[c][1,2,5]thiadiazol-5-amine (0.283 mmol, 1 equiv.), Na2CO3 (1.134 mmol, 4 equiv.) and Xanthphos (0.113 mmol, 0.4 equiv.) were added and degassed for 10 min. Pd2(dba)3 (0.113 mmol, 0.4 equiv.) was added and degassed once again for 10 min. Heated the reaction mixture at 115° C. for overnight. The reaction was cooled and filtered through small pad of celite. The filtrate obtained was concentrated to provide crude material. The crude material was purified by column chromatography through silica gel and MeOH: CHCl3 as eluent to afford 2-(6-(benzo[c][1,2,5]thiadiazol-5-ylamino)-4-(isopropylamino)pyridin-3-yl)-N-(3-hydroxypropyl)-5-methyloxazole-4-carboxamide [Example 90]. 1H NMR: 400 MHz, CD3OD: δ 1.42 (d, J=6.40 Hz, 6H), 1.83-1.84 (m, 2H), 2.71 (s, 3H), 3.51 (t, J=1.20 Hz, 2H), 3.72 (t, J=7.20 Hz, 2H), 3.81-3.83 (m, 1H), 6.28 (s, 1H), 7.67 (dd, J=2.00, 9.40 Hz, 1H), 7.89 (dd, J=9.60, 9.20 Hz, 1H), 8.47 (s, 1H), 8.64 (s, 1H). LC/MS: Ascentis Express C18, 5×2.1 mm-2.7 μm; Solvent A=2% ACN: 98% H2O: 10 mM NH4COOH; Solvent B=98% ACN: 2% H2O: 10 mM NH4COOH; gradient 0-100% B over 3 min; retention time: 1.896 min; LCMS (ES-API), m/z 466.0 (M−H). HPLC: Sunfire C18 (150×4.6 mm), 3.5 micron; Solvent A=5% ACN: 95% H2O: 0.05% TFA pH=2.5; Solvent B=95% ACN: 5% H2O: 0.05% TFA pH=2.5; gradient 0-100% B over 15 min (23 min run time); Flow rate: 1.0 μL/min; Retention time: 6.335 min; Purity: 98.7%.

後処理

  1. customdegassed for 10 min
  2. customdegassed once again for 10 min
  3. temperatureThe reaction was cooled
  4. filtrationfiltered through small pad of celite
  5. customThe filtrate obtained
  6. concentrationwas concentrated
  7. customto provide crude material
  8. customThe crude material was purified by column chromatography through silica gel and MeOH

出典と根拠

ORDレコード
ord-312b97aca3ba40fb9e43752229ab0845
出典データセット
uspto-grants-2016_01
特許番号
US09242975B2

反応ノート

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