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Water → 1-[1-({4-[(3-Chlorophenoxy)methyl]phenyl}carbonyl)azetidin-3-yl]-4-(1,3-thiazol-2-ylcarbonyl)piperazine

HRID 401669
ノート
印刷プレビュー

反応式

HRID 401669 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[O:5][CH2:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][CH:8]=1.[NH:19]1[CH2:22][CH:21]([N:23]2[CH2:28][CH2:27][N:26]([C:29]([C:31]3[S:32][CH:33]=[CH:34][N:35]=3)=[O:30])[CH2:25][CH2:24]2)[CH2:20]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O>CCN(CC)CC.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[O:5][CH2:6][C:7]1[CH:8]=[CH:9][C:10]([C:11]([N:19]2[CH2:20][CH:21]([N:23]3[CH2:24][CH2:25][N:26]([C:29]([C:31]4[S:32][CH:33]=[CH:34][N:35]=4)=[O:30])[CH2:27][CH2:28]3)[CH2:22]2)=[O:13])=[CH:14][CH:15]=1
参加物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 962WaterHCID 5846604-[(3-Chlorophenoxy)methyl]benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59625677(4-(Azetidin-3-yl)piperazin-1-yl)(thiazol-2-yl)methanone

生成物 1

HCID 497838661-[1-({4-[(3-Chlorophenoxy)methyl]phenyl}carbonyl)azetidin-3-yl]-4-(1,3-thiazol-2-ylcarbonyl)piperazine
収率 46.5%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒

実験手順

A mixture of compound 35d (77 mg, 0.29 mmol), compound 5e (108 mg, 0.38 mmol) and HATU (165 mg, 0.44 mmol) in Et3N (1 mL) and DMF (3 mL) was stirred for 18 h, and then poured into water (10 mL). The mixture was then extracted with EtOAc (3×). The combined organic extracts were washed with brine (2×), dried over Na2SO4, filtered, and concentrated under reduced pressure. The resultant residue was purified by flash column chromatography, eluting with 5% MeOH/CH2Cl2, to give compound 453 (67 mg). MS m/z (M+H+) 497.1. 1H NMR (CD3OD): δ 7.95 (d, J=2.0 Hz, 1H), 7.8 (d, J=2.0 Hz, 1H), 7.65 (d, J=8.1 Hz, 2H), 7.51 (d, J=8.1 Hz, 2H), 7.25 (t, J=8.0 Hz, 1H), 7.02 (s, 1H), 6.90-6.98 (m, 2H), 5.15 (s, 2H), 4.32-4.45 (m, 2H), 4.15-4.25 (m, 2H), 4.00-4.10 (m, 1H), 3.70-3.82 (br. s, 2H), 2.47 (br. s., 4H).

後処理

  1. extractionThe mixture was then extracted with EtOAc (3×)
  2. washThe combined organic extracts were washed with brine (2×)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resultant residue was purified by flash column chromatography
  7. washeluting with 5% MeOH/CH2Cl2

出典と根拠

ORDレコード
ord-ebca75bb872746d18b799403907f18ef
出典データセット
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08741887B2

反応ノート

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