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

HRID 1842595노트

반응식

HRID 1842595 반응식
[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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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)

후처리

  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)

출처 및 근거

ORD 기록
ord-d8e259913f4749279045a11206275a8a
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946237B2

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