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Cesium carbonate → (R)-5-chloro-2-fluoro-4-(9'-isopropyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepine]-2'-ylamino)-N-(1-methylpyrrolidin-3-yl)benzamide

HRID 2234307
ノート
印刷プレビュー

反応式

HRID 2234307 の反応式
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:6]([CH3:19])[C:7](=[O:18])[C:8]3([CH2:17][CH2:16]3)[CH2:9][N:10]([CH:13]([CH3:15])[CH3:14])[C:11]=2[N:12]=1.[NH2:20][C:21]1[C:35]([Cl:36])=[CH:34][C:24]([C:25]([NH:27][C@@H:28]2[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29]2)=[O:26])=[C:23]([F:37])[CH:22]=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:36][C:35]1[C:21]([NH:20][C:2]2[N:3]=[CH:4][C:5]3[N:6]([CH3:19])[C:7](=[O:18])[C:8]4([CH2:17][CH2:16]4)[CH2:9][N:10]([CH:13]([CH3:15])[CH3:14])[C:11]=3[N:12]=2)=[CH:22][C:23]([F:37])=[C:24]([CH:34]=1)[C:25]([NH:27][C@@H:28]1[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29]1)=[O:26]
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 686875884-amino-5-chloro-2-fluoro-N-[(3R)-1-methylpyrrolidin-3-yl]benzamide2 回HCID 866175592'-chloro-9'-isopropyl-5'-methyl-8',9'-dihydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepin]-6'(5'H)-one2 回

生成物 1

HCID 68682696
(R)-5-chloro-2-fluoro-4-(9'-isopropyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepine]-2'-ylamino)-N-(1-methylpyrrolidin-3-yl)benzamide
収率 90%

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′-isopropyl-5′-methyl-8′,9′-dihydrospiro[cyclopropane-1,7′-pyrimido[5,4-b][1,4]diazepin]-6′(5′H)-one (Intermediate 208; 88 mg, 0.32 mmol), 4-amino-5-chloro-2-fluoro-N-[(3R)-1-methylpyrrolidin-3-yl]benzamide (Intermediate 207; 101 mg, 0.36 mmol) and XANTPHOS (17 mg, 0.03 mmol) were dissolved in 1,4-dioxane (7.5 mL). Caesium carbonate (229 mg, 0.65 mmol) was added and the system purged with a stream of nitrogen for 15 minutes before tris(dibenzylideneacetone) palladium (II) (18 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 washed with methanol and eluted with ammonia in methanol. Product containing fractions were concentrated and purified by column chromatography (2.5% 7N ammonia in MeOH/DCM) to yield the title compound as a pale yellow foam (148 mg, 90%).

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 washed with methanol
  7. washeluted with ammonia in methanol
  8. additionProduct containing fractions
  9. concentrationwere concentrated
  10. custompurified by column chromatography (2.5% 7N ammonia in MeOH/DCM)

出典と根拠

ORDレコード
ord-ba1f5044f6df41228d2cb65bdc8df924
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

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