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Acetyl chloride → 2-[5-(6-Methyl-pyrimidin-4-yl)-indan-1-yl]-2,7-diaza-spiro[3.5]nonane-dihydrochloride

HRID 1913457
ノート
印刷プレビュー

反応式

HRID 1913457 の反応式
C([Cl:4])(=O)C.C(OC([N:12]1[CH2:36][CH2:35][C:15]2([CH2:18][N:17]([C@H:19]3[C:27]4[C:22](=[CH:23][C:24]([C:28]5[CH:33]=[C:32]([CH3:34])[N:31]=[CH:30][N:29]=5)=[CH:25][CH:26]=4)[CH2:21][CH2:20]3)[CH2:16]2)[CH2:14][CH2:13]1)=O)(C)(C)C>CO>[ClH:4].[ClH:4].[CH3:34][C:32]1[N:31]=[CH:30][N:29]=[C:28]([C:24]2[CH:23]=[C:22]3[C:27](=[CH:26][CH:25]=2)[CH:19]([N:17]2[CH2:18][C:15]4([CH2:35][CH2:36][NH:12][CH2:13][CH2:14]4)[CH2:16]2)[CH2:20][CH2:21]3)[CH:33]=1
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

4

反応物 2

HCID 6367Acetyl chlorideHCID 674086712-[(R)-5-(6-Methylpyrimidin-4-yl)-indan-1-yl]-2,7-diazaspiro[3.5]nonane-7-carboxylic acid tert-butyl ester

生成物 1

HCID 674060892-[5-(6-Methyl-pyrimidin-4-yl)-indan-1-yl]-2,7-diaza-spiro[3.5]nonane-dihydrochloride収率 102.4%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒2 回

反応条件

温度
0 °C

実験手順

A flask containing methanol (100 mL) was cooled to 0° C. The solution was then charged dropwise with acetyl chloride (16.38 mL, 230.11 mmol) over 1 h maintaining a temperature of 10° C. The resulting mixture was charged with 2-[(R)-5-(6-methylpyrimidin-4-yl)-indan-1-yl]-2,7-diazaspiro[3.5]nonane-7-carboxylic acid tert-butyl ester (3-1f, 10.0 g, 23.01 mmol) in methanol (50 mL). The resulting mixture was stirred while warming to 20° C. for 18 h. HPLC after 18 h indicated disappearance of starting material. The resulting slurry was concentrated under reduced pressure removing approximately half the total volume. Isopropylacetate (50 mL) was then added and the resulting slurry was stirred for 1 h at 20° C. The solid was filtered and washed with isopropyl acetate (20 mL) under nitrogen. The solids were dried using a filter press with a nitrogen stream followed by drying under vacuum at 45° C. to afford 2-[5-(6-methyl-pyrimidin-4-yl)-indan-1-yl]-2,7-diaza-spiro[3.5]nonane-dihydrochloride (3-1g, 9.6 g, 98%). MS (ES+) 335.2 (M+H)+. 1H NMR (CD3OD) δ 2.16-2.23 (m, 5H), 2.59 (br s, 1H), 2.78-2.80 (m, 3H), 3.12 (br s, 1H), 3.19-3.24 (m, 4H), 3.37-3.49 (m, 1H), 4.14-4.23 (m, 3H), 4.49 (br s, 1H), 5.11 (br s, 1H), 7.84 (d, 1H), 8.30-8.34 (m, 2H), 8.46 (s, 1H), 9.36 (s, 1H).

後処理

  1. temperaturemaintaining a temperature of 10° C
  2. temperaturewhile warming to 20° C. for 18 h
  3. concentrationThe resulting slurry was concentrated under reduced pressure
  4. customremoving approximately half the total volume
  5. additionIsopropylacetate (50 mL) was then added
  6. stirringthe resulting slurry was stirred for 1 h at 20° C
  7. filtrationThe solid was filtered
  8. washwashed with isopropyl acetate (20 mL) under nitrogen
  9. customThe solids were dried
  10. customby drying under vacuum at 45° C.

出典と根拠

ORDレコード
ord-db11fc641ec547f1b3f95671749d2c14
出典データセット
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08609680B2

反応ノート

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