Triethylamine → 5-Oxo-4-pyridine-3-yl-7-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-4,5-dihydro-2-thia-4-aza-indene-6-carbonitrile

HRID 902515노트

반응식

HRID 902515 반응식
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.C(N(CC)CC)C.[O:17]=[C:18]1[C:26]([C:27]#[N:28])=[C:25]([N:29]2[CH2:34][CH2:33][N:32]([C:35]([C:37]3[S:38][CH:39]=[CH:40][CH:41]=3)=[O:36])[CH2:31][CH2:30]2)[C:24]2[C:20](=[CH:21][S:22][CH:23]=2)[NH:19]1>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Cu+2]>[O:17]=[C:18]1[C:26]([C:27]#[N:28])=[C:25]([N:29]2[CH2:30][CH2:31][N:32]([C:35]([C:37]3[S:38][CH:39]=[CH:40][CH:41]=3)=[O:36])[CH2:33][CH2:34]2)[C:24]2[C:20](=[CH:21][S:22][CH:23]=2)[N:19]1[C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1

참가 물질

6

반응물 3

HCID 8471TriethylamineHCID 27343783-Pyridinylboronic acidHCID 597021165-Oxo-7-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-4,5-dihydro-2-thia-4-aza-indene-6-carbonitrile

생성물 1

HCID 597020485-Oxo-4-pyridine-3-yl-7-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-4,5-dihydro-2-thia-4-aza-indene-6-carbonitrile

시약·촉매·용매 2

HCID 8895Cupric acetate촉매HCID 6228Dimethylformamide용매

실험 절차

Cu(OAc)2 (363 mg, 2 mmol), pyridine-3-boronic acid (614 mg, 5 mmol), and triethylamine (560 μL, 4 mmol) were added to a solution of 5-oxo-7-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-4,5-dihydro-2-thia-4-aza-indene-6-carbonitrile (47) (370 mg, 1 mmol) in wet DMF (DMF:H2O::9:1) stirred at room temperature. The solution was further stirred at room temperature for 24 h. The solution was passed through a bed of celite and the solvent was evaporated. The residue was suspended in water and extracted by CH2Cl2. The combined organic phase was partitioned with 10% aqueous HCl solution. The aqueous phase was separated and the pH was adjusted to 5 by 4 N NaOH solution. Then, a saturated solution of NaHCO3 was added until the pH reached to 8. The solids formed were filtered, washed by water, and dried under vacuum at 70° C. to get 5-oxo-4-pyridine-3-yl-7-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-4,5-dihydro-2-thia-4-aza-indene-6-carbonitrile as white solids. Yield 243 mg (54%); MP 282° C.; 1H NMR (400 MHz, DMSO-d6) δ 3.99 (m, 8H), 6.42 (d, J=2.8 Hz, 1H), 7.18 (dd, J=4.0, 4.8 Hz, 1H), 7.52 (d, J=2.8 Hz, 1H), 7.64 (dd, J=4.8, 8.0 Hz, 1H), 7.81 (d, J=4.8 Hz, 1H), 7.88 (dm, 1H), 8.47 (d, J=3.2 Hz, 1H), 8.58 (d, J=2.0 Hz, 1H), 8.71 (d, J=3.6 Hz, 1H) ppm; MS m/z=448 amu (M++1). Anal. (C22H17N5O2S2) N.

후처리

  1. stirringThe solution was further stirred at room temperature for 24 h
  2. customthe solvent was evaporated
  3. extractionextracted by CH2Cl2
  4. customThe combined organic phase was partitioned with 10% aqueous HCl solution
  5. customThe aqueous phase was separated
  6. additionThen, a saturated solution of NaHCO3 was added until the pH
  7. customThe solids formed
  8. filtrationwere filtered
  9. washwashed by water
  10. customdried under vacuum at 70° C.

출처 및 근거

ORD 기록
ord-8d609d02546d41ed869872e30a40d9f5
출처 데이터셋
uspto-grants-2008_04
특허 번호
US07365200B2

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