Diethyl Ether → 4-(Azetidin-1-ylmethyl)piperidine-1-carboxylic acid {6-[2-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyrimidin-4-yl}amide

HRID 493000ノート

反応式

HRID 493000 の反応式
[NH2:1][C:2]1[CH:28]=[CH:27][C:5]([O:6][C:7]2[N:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][CH:19]([CH2:22][N:23]4[CH2:26][CH2:25][CH2:24]4)[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[C:4]([F:29])[CH:3]=1.[C@]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[C:45]1([CH2:51][C:52]([N:54]=[C:55]=[S:56])=[O:53])[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.C(OCC)C>C(O)C.C1(C)C=CC=CC=1.CCCCCC>[F:29][C:4]1[CH:3]=[C:2]([NH:1][C:55]([NH:54][C:52](=[O:53])[CH2:51][C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)=[S:56])[CH:28]=[CH:27][C:5]=1[O:6][C:7]1[N:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]2[CH2:21][CH2:20][CH:19]([CH2:22][N:23]3[CH2:26][CH2:25][CH2:24]3)[CH2:18][CH2:17]2)=[O:15])[CH:8]=1

参加物

8

反応物 4

HCID 3283Diethyl EtherHCID 218580(1S)-(+)-Camphor-10-sulphonic acidHCID 12454157Phenylacetyl isothiocyanateHCID 576773324-(Azetidin-1-ylmethyl)piperidine-1-carboxylic acid [6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]amide

生成物 1

HCID 576775684-(Azetidin-1-ylmethyl)piperidine-1-carboxylic acid {6-[2-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyrimidin-4-yl}amide

試薬・触媒・溶媒 3

HCID 702Ethanol溶媒HCID 1140Toluene溶媒HCID 8058Hexane溶媒

実験手順

4-(Azetidin-1-ylmethyl)piperidine-1-carboxylic acid [6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]amide (110 mg) was dissolved in ethanol (3 ml) under a nitrogen atmosphere, and then (S)-(+)-10-camphorsulfonic acid (64 mg) was added thereto, followed by stirring for 5 min. A 0.25 M solution of phenylacetyl isothiocyanate in toluene (1.65 ml) was added thereto, followed by stirring for 1 hr. The reaction mixture was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (30 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (30 ml), water (30 ml), brine (30 ml) in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; heptane:ethyl acetate=1:8, then ethyl acetate). Fractions containing the target compound were concentrated under reduced pressure to give a residue, to which diethyl ether (4 ml) and hexane (4 ml) were then added to suspend. The solid was filtered off, and dried under aeration to provide the titled compound (76.1 mg) as white powder.

後処理

  1. stirringby stirring for 1 hr
  2. customThe reaction mixture was partitioned between ethyl acetate (50 ml)
  3. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (30 ml), water (30 ml), brine (30 ml) in this order
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated
  6. customto give a residue, which
  7. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent
  8. additionFractions containing the target compound
  9. concentrationwere concentrated under reduced pressure
  10. customto give a residue
  11. filtrationThe solid was filtered off
  12. customdried under aeration

出典と根拠

ORDレコード
ord-623298ecb58a4942a4afc0f9d8e99777
出典データセット
uspto-grants-2009_05
特許番号
US07531532B2

反応ノート

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