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(5-Cyano-1-benzothiophen-2-yl)boronic acid → HCID 90284814、化合物

HRID 2173079
ノート
印刷プレビュー

反応式

HRID 2173079 の反応式
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C@H:14]([NH:15][C:16]2[N:21]=[C:20](Cl)[C:19]3[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=3[C:17]=2[F:34])[CH2:13][CH2:12][O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:35]([C:37]1[CH:48]=[CH:47][C:40]2[S:41][C:42](B(O)O)=[CH:43][C:39]=2[CH:38]=1)#[N:36]>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O.C([O-])(O)=O.[Na+].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>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C@H:14]([NH:15][C:16]2[N:21]=[C:20]([C:42]3[S:41][C:40]4[CH:47]=[CH:48][C:37]([C:35]#[N:36])=[CH:38][C:39]=4[CH:43]=3)[C:19]3[C:23](=[O:33])[N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25][C:18]=3[C:17]=2[F:34])[CH2:13][CH2:12][O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 2

HCID 53398611(5-Cyano-1-benzothiophen-2-yl)boronic acidHCID 86654748tert-Butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate

生成物 1

HCID 90284814HCID 90284814、化合物

試薬・触媒・溶媒 5

HCID 178418397HCID 178418397、化合物触媒
HCID 8857
Ethyl Acetate
溶媒
HCID 10340Sodium Carbonate溶媒
HCID 312751,4-Dioxane溶媒
HCID 516892Sodium Bicarbonate溶媒

実験手順

A solution of tert-butyl 6-((3R,4R)-3-(tert-butoxycarbonylamino)tetrahydro-2H-pyran-4-ylamino)-4-chloro-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate (100 mg, 0.200 mmol), 5-cyanobenzo[b]thiophen-2-ylboronic acid (40.5 mg, 0.200 mmol) and tetrakis(triphenylphosphine)palladium(0) (231 mg, 0.200 mmol) in dioxane and saturated aqueous Na2CO3 (3:5, 6 mL) was heated to 120° C. in a microwave for 30 minutes. The reaction mixture was diluted with EtOAc (50 mL) and saturated aqueous NaHCO3 (100 mL). The organic layer was separated and the aqueous layer was washed with EtOAc (50 mL). The organic layers were combined, dried over Na2SO4, and the solvent was removed in vacuo to give the intermediate, tert-butyl 6-(((3R,4R)-3-((tert-butoxycarbonyl)amino)tetrahydro-2H-pyran-4-yl)amino)-4-(5-cyanobenzo[b]thiophen-2-yl)-7-fluoro-3-oxo-1H-pyrrolo[3,4-c]pyridine-2(3H)-carboxylate. The intermediate was dispersed in TFA and DCM (1:1, 10 mL) and the mixture was stirred at room temperature for 60 minutes. The mixture was concentrated, reconstituted in MeOH and DCM (10.0 mL) and purified via preparative HPLC eluting with a gradient of 10-25% ACN (0.035% TFA) and H2O (0.05% TFA). The collected fractions were combined and diluted with EtOAc (50 mL) and saturated aqueous NaHCO3 (100 mL). The organic layer was separated and the aqueous layer was washed with EtOAc (50 mL). The organic layers were combined, dried over Na2SO4, and the solvent was removed in vacuo to give the title compound (26 mg, 31%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.78 (dd, J=13.42, 4.15 Hz, 1H), 1.87-2.05 (m, 1H), 3.17-3.25 (m, 1H), 3.45-3.57 (m, 1H), 3.67 (d, J=10.25 Hz, 1H), 3.80 (br s, 1H), 3.91 (d, J=11.23 Hz, 1H), 4.26 (d, J=4.39 Hz, 1H), 4.43 (s, 2H), 7.00 (d, J=6.35 Hz, 1H), 7.72 (dd, J=8.30, 1.46 Hz, 1H), 8.20 (d, J=8.30 Hz, 1H), 8.47 (d, J=1.46 Hz, 1H), 8.61 (s, 1H), 9.50 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C21H18FN5O2S, 424. found, 424.

後処理

  1. customThe organic layer was separated
  2. washthe aqueous layer was washed with EtOAc (50 mL)
  3. dry with materialdried over Na2SO4
  4. customthe solvent was removed in vacuo

出典と根拠

ORDレコード
ord-c2133e1f2c5b4b8a92b6baf4dce5b37d
出典データセット
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09056873B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート