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Cesium carbonate → 5-chloro-4-(9'-cyclopentyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepine]-2'-ylamino)-2-fluoro-N-(1-methyl-4-piperidyl)benzamide

HRID 2234322
ノート
印刷プレビュー

反応式

HRID 2234322 の反応式
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:6]([CH3:21])[C:7](=[O:20])[C:8]3([CH2:19][CH2:18]3)[CH2:9][N:10]([CH:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[C:11]=2[N:12]=1.[NH2:22][C:23]1[C:38]([Cl:39])=[CH:37][C:26]([C:27]([NH:29][CH:30]2[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]2)=[O:28])=[C:25]([F:40])[CH:24]=1.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.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.[Pd+2].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[Cl:39][C:38]1[C:23]([NH:22][C:2]2[N:3]=[CH:4][C:5]3[N:6]([CH3:21])[C:7](=[O:20])[C:8]4([CH2:19][CH2:18]4)[CH2:9][N:10]([CH:13]4[CH2:14][CH2:15][CH2:16][CH2:17]4)[C:11]=3[N:12]=2)=[CH:24][C:25]([F:40])=[C:26]([CH:37]=1)[C:27]([NH:29][CH:30]1[CH2:31][CH2:32][N:33]([CH3:36])[CH2:34][CH2:35]1)=[O:28]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 579699392-chloro-9-cyclopentyl-8,9-dihydro-5-methylspiro[5H-pyrimido[4,5-b][1,4]diazepine-7,1'-cyclopropan]-6(7H)-one2 回HCID 686824664-amino-5-chloro-2-fluoro-N-(1-methyl-4-piperidyl)benzamide2 回

生成物 1

HCID 68684381
5-chloro-4-(9'-cyclopentyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepine]-2'-ylamino)-2-fluoro-N-(1-methyl-4-piperidyl)benzamide
収率 60%

試薬・触媒・溶媒 2

HCID 9897284tris(dibenzylideneacetone) palladium (II)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

2′-chloro-9′-cyclopentyl-5′-methyl-8′,9′-dihydrospiro[cyclopropane-1,7′-pyrimido[5,4-b][1,4]diazepin]-6′(5′H)-one (Intermediate 130; 85 mg, 0.30 mmol), 4-amino-5-chloro-2-fluoro-N-(1-methyl-4-piperidyl)benzamide (Intermediate 173; 101 mg, 0.33 mmol) and XANTPHOS (16 mg, 0.03 mmol) were dissolved in 1,4-dioxane (7.5 mL). Caesium carbonate (210 mg, 0.59 mmol) was added and the system purged with a stream of nitrogen for 15 minutes before tris(dibenzylideneacetone) palladium (II) (17 mg, 0.02 mmol) was added. The apparatus was evacuated and backfilled with nitrogen (×3) and then heated at 100° C. for 3 hours. The mixture was cooled, filtered and the filtrate absorbed on to an SCX column, which was subsequently washed with methanol and eluted with ammonia in methanol. Product containing fractions were concentrated and purified by base modified reverse phase preparative HPLC to yield the title compound as a white solid (100 mg, 60%).

後処理

  1. additionwas added
  2. customThe apparatus was evacuated
  3. temperatureThe mixture was cooled
  4. filtrationfiltered
  5. customthe filtrate absorbed on to an SCX column, which
  6. washwas subsequently washed with methanol
  7. washeluted with ammonia in methanol
  8. additionProduct containing fractions
  9. concentrationwere concentrated
  10. custompurified by base modified reverse phase preparative HPLC

出典と根拠

ORDレコード
ord-a9934bc8fd5446f5bd38532c09462211
出典データセット
uspto-grants-2010_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07709471B2

反応ノート

読み込み中…

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