Trifluoroacetic acid → US9611269, Example 22

HRID 571505노트

반응식

HRID 571505 반응식
[C:1]([CH2:3][C:4]1([N:18]2[CH:22]=[C:21]([C:23]3[C:24]4[CH:31]=[CH:30][N:29](COCC[Si](C)(C)C)[C:25]=4[N:26]=[CH:27][N:28]=3)[CH:20]=[N:19]2)[CH2:7][N:6]([C:8]2[CH:16]=[CH:15][C:11]([C:12](O)=[O:13])=[C:10]([F:17])[CH:9]=2)[CH2:5]1)#[N:2].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.[F:73][C:74]([F:79])([F:78])[C@@H:75]([NH2:77])[CH3:76].FC(F)(F)C(O)=O>ClCCCl>[C:1]([CH2:3][C:4]1([N:18]2[CH:22]=[C:21]([C:23]3[C:24]4[CH:31]=[CH:30][NH:29][C:25]=4[N:26]=[CH:27][N:28]=3)[CH:20]=[N:19]2)[CH2:7][N:6]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([NH:77][C@@H:75]([CH3:76])[C:74]([F:79])([F:78])[F:73])=[O:13])=[C:10]([F:17])[CH:9]=2)[CH2:5]1)#[N:2]

참가 물질

7

반응물 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10964447(S)-1,1,1-trifluoropropan-2-amineHCID 711436084-{3-(cyanomethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-2-fluorobenzoic acid

생성물 1

HCID 71155372US9611269, Example 22

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

실험 절차

To a solution of 4-{3-(cyanomethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-2-fluorobenzoic acid (25 mg, 0.046 mmol) (Example 15, Step 2) and N,N-diisopropylethylamine (24 μL, 0.14 mmol) in 1,2-dichloroethane (0.5 mL) was added sequentially N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (26 mg, 0.068 mmol) and (2S)-1,1,1-trifluoropropan-2-amine (12 mg, 0.11 mmol). After stirring at ambient temperature for 1.5 h, trifluoroacetic acid (0.5 mL) was added to the reaction mixture and stirring was continued for 1 h. The volatiles were removed in-vacuo and the residue was azeotropically washed with acetonitrile (3×3 mL). The resulting residue was dissolved in methanol (1 mL) and to this was added ammonium hydroxide (0.1 mL) and ethylenediamine (0.020 mL) and the reaction mixture was stirred at ambient temperature for 1 hour. The crude reaction mixture was subjected to RP-HPLC to afford the desired product. LCMS (M+H)+: m/z=513.1. 1H NMR (500 MHz, DMSO-d6): δ 12.64 (s, 1H), 9.06 (s, 1H), 8.85 (s, 1H), 8.56 (s, 1H), 8.33 (dd, J=8.9, 1.8 Hz, 1H), 7.79 (s, 1H), 7.52 (t, J=8.5 Hz, 1H), 7.23 (s, 1H), 6.47 (s, 1H), 6.45-6.42 (m, 1H), 4.83-4.75 (m, 1H), 4.59 (dd, J=8.9, 1.7 Hz, 2H), 4.34 (d, J=8.9 Hz, 2H), 3.77 (s, 2H), 1.31 (d, J=7.1 Hz, 3H).

후처리

  1. stirringstirring
  2. waitwas continued for 1 h
  3. customThe volatiles were removed in-vacuo
  4. washthe residue was azeotropically washed with acetonitrile (3×3 mL)
  5. dissolutionThe resulting residue was dissolved in methanol (1 mL)
  6. additionto this was added ammonium hydroxide (0.1 mL) and ethylenediamine (0.020 mL)
  7. stirringthe reaction mixture was stirred at ambient temperature for 1 hour
  8. customThe crude reaction mixture

출처 및 근거

ORD 기록
ord-e79a612017f54973a32a8c1d91783f32
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09023840B2

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