Formic Acid → HCID 117665878, 화합물

HRID 630696노트

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HRID 630696 반응식
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][C:10]2[N:14]3[CH:15]=[C:16]([O:19][C@H:20]4[C:29]5[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=5)[C@@H:23]([NH2:30])[CH2:22][CH2:21]4)[CH:17]=[CH:18][C:13]3=[N:12][N:11]=2)[CH2:4][CH2:3]1.ClC(Cl)(Cl)C[O:34][C:35](=[O:53])[NH:36][C:37]1[N:38]([C:46]2[CH:51]=[CH:50][C:49]([CH3:52])=[CH:48][CH:47]=2)[N:39]=[C:40]([C:42]([CH3:45])([CH3:44])[CH3:43])[CH:41]=1.CCN(C(C)C)C(C)C.C(O)=O>O1CCOCC1>[CH:35]([OH:53])=[O:34].[C:42]([C:40]1[CH:41]=[C:37]([NH:36][C:35]([NH:30][C@@H:23]2[C:24]3[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=3)[C@H:20]([O:19][C:16]3[CH:17]=[CH:18][C:13]4[N:14]([C:10]([CH2:9][CH2:8][N:5]5[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]5)=[N:11][N:12]=4)[CH:15]=3)[CH2:21][CH2:22]2)=[O:34])[N:38]([C:46]2[CH:51]=[CH:50][C:49]([CH3:52])=[CH:48][CH:47]=2)[N:39]=1)([CH3:45])([CH3:43])[CH3:44]

참가 물질

6

반응물 4

HCID 284Formic AcidHCID 81531DiisopropylethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 86686949HCID 86686949, 화합물

생성물 1

HCID 117665878HCID 117665878, 화합물

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

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온도
60 °C

실험 절차

Intermediate 2c (85.0 mg, 0.21 mmol) was dissolved in 1,4-dioxane (2 mL) and (5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (Synthetic Communications, 2009, 39, 3999-4009, which is incorporated herein by reference in its entirety; 96.0 mg, 0.24 mmol) and DIPEA (75.0 μl, 0.43 mmol) were added. The reaction was heated to 60° C. for 18 h. After cooling, the mixture was partitioned between EtOAc (50 mL) and water (50 mL), and extracted into EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4) and evaporated in vacuo. The residue was purified by FCC, using 0-10% [2M NH3 in MeOH] in DCM, then further purified by HPLC (C, 18 X-select column, 10-40% MeCN in H2O, 0.1% formic acid) to give the title compound mainly as formic acid salt (43.0 mg, 0.065 mmol, 31%). LCMS (Method 5) Rt 3.54 mins, m/z 662 [MH+]. 1H NMR (400 MHz, d4-MeOD): 1.30 (9H, s), 1.90-2.05 (2H, m), 2.06-2.15 (1H, m), 2.20-2.30 (1H, m), 2.38 (3H, s), 2.40 (3H, s), 2.55-2.75 (8H, br s), 2.90-2.95 (2H, t, J 7.4), 3.29-3.32 (2H, t, J 7.4), 4.86-4.92 (1H, dd, J 8.8, 5.6), 5.43-5.47 (1H, t, J 4.2), 6.33 (1H, s), 7.21-7.35 (11H, m), 7.60-7.64 (1H, d, J 9.9), 8.07-8.09 (1H, d, J 1.9), 8.40-8.50 (0.4H, br s, formate).

후처리

  1. temperatureAfter cooling
  2. customthe mixture was partitioned between EtOAc (50 mL) and water (50 mL)
  3. extractionextracted into EtOAc (3×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated in vacuo
  7. customThe residue was purified by FCC
  8. customfurther purified by HPLC (C, 18 X-select column, 10-40% MeCN in H2O, 0.1% formic acid)

출처 및 근거

ORD 기록
ord-67dcba1ad05143cf8984eb0acf729f2c
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09315503B2

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