Diisopropylethylamine → tert-Butyl[(1R,2R)-2-{[(4-bromo-5 ethylthiophen-2-yl)carbonyl]amino}-3,3-difluorocyclohexyl]carbamate

HRID 1842595ノート

反応式

HRID 1842595 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([C:9]([OH:11])=O)[S:5][C:6]=1[CH2:7][CH3:8].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:39][C@H:40]1[C:45]([F:47])([F:46])[CH2:44][CH2:43][CH2:42][C@H:41]1[NH:48][C:49](=[O:55])[O:50][C:51]([CH3:54])([CH3:53])[CH3:52].C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[C:51]([O:50][C:49](=[O:55])[NH:48][C@@H:41]1[CH2:42][CH2:43][CH2:44][C:45]([F:47])([F:46])[C@@H:40]1[NH:39][C:9]([C:4]1[S:5][C:6]([CH2:7][CH3:8])=[C:2]([Br:1])[CH:3]=1)=[O:11])([CH3:54])([CH3:52])[CH3:53]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 37663724-Bromo-5-ethylthiophene-2-carboxylic acidHCID 59603811tert-Butyl ((1R,2R)-2-amino-3,3-difluorocyclohexyl)carbamate

生成物 1

HCID 89750990tert-Butyl[(1R,2R)-2-{[(4-bromo-5 ethylthiophen-2-yl)carbonyl]amino}-3,3-difluorocyclohexyl]carbamate収率 78.6%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

4-Bromo-5-ethylthiophene-2-carboxylic acid (1.00 g, 4.25 mmol) and BOP (5.64 g, 12.8 mmol) were dissolved in DMF (42.5 mL) and stirred at room temperature for 5 min. To the reaction solution was added tert-butyl [(1R,2R)-2-amino-3,3-difluorocyclohexyl]carbamate (1.07 g, 4.25 mmol) and diisopropylethyl amine (1.11 mL, 6.38 mmol) and the reaction stirred at room temperature for 64 h. The reaction mixture was diluted with ethyl acetate and washed with water 3×. The organic layer was collected, dried with sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (0-50% EtOAc/Hex) to give the title compound (1.56 g, 3.34 mmol). LRMS (APCI) calc'd for (C18H25BrF2N2O3S) [M+H]+, 467.1; found 466.9. 1H NMR (CDCl3, 500 MHz) δ 7.32 (s, 1H), 6.28 (s, 1H), 4.90 (s, 1H), 4.54 (s, 1H), 4.29 (s, 1H), 2.81 (q, J=7.5, 2H), 2.22 (m, 1H), 1.88 (m, 1H), 1.81 (m, 1H), 1.69 (m, 1H), 1.59 (m, 1H), 1.46 (s, 9H), 1.41 (m, 1H), 1.28 (t, J=7.3, 3H)

後処理

  1. stirringthe reaction stirred at room temperature for 64 h
  2. washwashed with water 3×
  3. customThe organic layer was collected
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography (0-50% EtOAc/Hex)

出典と根拠

ORDレコード
ord-d8e259913f4749279045a11206275a8a
出典データセット
uspto-grants-2015_02
特許番号
US08946237B2

反応ノート

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