Triethylamine → 4-(4-fluoro-3-(3H-spiro[isobenzofuran-1,4'-piperidine]-1'-ylcarbonyl)benzyl)phthalazin-1(2H)-one

HRID 1091699노트

반응식

HRID 1091699 반응식
[F:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[NH:14][N:13]=2)=[CH:7][C:3]=1[C:4](O)=[O:5].Cl.[NH:24]1[CH2:29][CH2:28][C:27]2([C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH2:31][O:30]2)[CH2:26][CH2:25]1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C)C(=O)C>[F:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[NH:14][N:13]=2)=[CH:7][C:3]=1[C:4]([N:24]1[CH2:29][CH2:28][C:27]2([C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH2:31][O:30]2)[CH2:26][CH2:25]1)=[O:5]

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 225093303H-spiro(2-benzofuran-1,4'-piperidine) hydrochlorideHCID 248117402-Fluoro-5-[(4-oxo-3,4-dihydrophthalazin-1-yl)methyl]benzoic acid

생성물 1

HCID 441977814-(4-fluoro-3-(3H-spiro[isobenzofuran-1,4'-piperidine]-1'-ylcarbonyl)benzyl)phthalazin-1(2H)-one수율 52.4%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

실험 절차

A solution of 2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid (1) (144 mg, 0.48 mmol) and 3H-spiro[isobenzofuran-1,4′-piperidine]hydrochloride (109 mg, 0.48 mmol) in N,N-dimethylacetamide (2 mL) was treated with triethylamine (0.168 mL, 1.21 mmol) and O-Benzotriazol-1-yl-N,N,N′,N′-tetra-methyluronium hexafluorophosphate (256 mg, 0.68 mmol). The resulting mixture was stirred at ambient temperature for 5 hours, before being filtered and purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 0.1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness and lyophilised to afford the desired compound as a white solid (118 mg, 52.1% yield); 1H NMR (400.132 MHz, DMSO) δ 1.53-1.62 (2H, m), 1.73-1.83 (3H, m), 1.91-1.99 (1H, m), 3.10-3.18 (1H, m), 4.40 (2H, s), 4.54-4.60 (1H, m), 5.03-5.11 (2H, m), 7.26-7.37 (5H, m), 7.45-7.50 (2H, m), 7.83-7.93 (2H, m), 8.02 (1H, d), 8.30 (1H, d), 12.13-12.59 (1H, br s); m/z (LC-MS, ESI+), RT=2.14 (M+H 470.9).

후처리

  1. filtrationbefore being filtered
  2. custompurified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  3. additionFractions containing the desired compound
  4. customwere evaporated to dryness

출처 및 근거

ORD 기록
ord-6f4301f5c3704090ace2a11875c36c31
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129380B2

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