Triethylamine → N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-(2-methyl-2H-tetrazol-5-yl)phenethoxy)propanamide

HRID 909902노트

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HRID 909902 반응식
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[CH3:19][O:20][CH:21]([O:30][CH3:31])[CH2:22][NH:23][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.[CH3:32][N:33]1[N:37]=[N:36][C:35]([C:38]2[CH:39]=[C:40]([CH:49]=[CH:50][CH:51]=2)[CH2:41][CH2:42][O:43][CH2:44][CH2:45][C:46](O)=[O:47])=[N:34]1.C(N(CC)CC)C>C1COCC1.C(#N)C.C(OCC)(=O)C>[CH:24]1([N:23]([CH2:22][CH:21]([O:30][CH3:31])[O:20][CH3:19])[C:46](=[O:47])[CH2:45][CH2:44][O:43][CH2:42][CH2:41][C:40]2[CH:49]=[CH:50][CH:51]=[C:38]([C:35]3[N:36]=[N:37][N:33]([CH3:32])[N:34]=3)[CH:39]=2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 3024915N-(2,2-dimethoxyethyl)cyclohexanamineHCID 59290424HCID 59290424, 화합물

생성물 1

HCID 59290471N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-(2-methyl-2H-tetrazol-5-yl)phenethoxy)propanamide

시약·촉매·용매 3

HCID 6342Acetonitrile용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
25 °C

실험 절차

A solution of T3P (1.91 mL) dissolved in THF (1.57M) was added in one portion to a stirred solution of N-(2,2-dimethoxyethyl)cyclohexanamine (0.33 mL), 3-(3-(2-methyl-2H-tetrazol-5-yl)phenethoxy)propanoic acid [Example 7, Step iii)] (0.41 g) and triethylamine (2.51 mL) in acetonitrile (5 mL) at 25° C. The resulting solution was stirred at 25° C. for 15 min. The reaction mixture was diluted with ethyl acetate (50 mL), and washed with saturated sodium hydrogen carbonate (20 mL). The organic layer was dried over magnesium sulfate, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 20-100% ethyl acetate in isohexane, then elution gradient 0-10% methanol in ethyl acetate to afford the subtitled compound (0.66 g). 1H NMR (400 MHz, CD3OD) δ 7.97-7.93 (m, 1H), 7.92-7.89 (m, 1H), 7.43-7.33 (m, 2H), 4.52 and 4.36 (2×t, J=5.3 Hz, 1H), 4.40 and 4.39 (2×s, 3H), 4.04-3.95 and 3.69-3.60 (2×m, 1H), 3.75-3.66 (m, 4H), 3.33 (s, 6H), 3.25 (d, J=4.9 Hz, 2H), 2.94-2.88 (m, 2H), 2.67-2.61 (m, 2H), 1.79-1.00 (m, 10H), a ˜1:1 mixture of rotamers is observed.

후처리

  1. washwashed with saturated sodium hydrogen carbonate (20 mL)
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified by flash silica chromatography, elution gradient 20-100% ethyl acetate in isohexane
  7. washelution gradient 0-10% methanol in ethyl acetate

출처 및 근거

ORD 기록
ord-3ce2e79ee235408ebe4eb0e55c7b333c
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08017602B2

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