Sodium Hydroxide → 6-((R)-3-hydroxypyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinic acid

HRID 73750노트

반응식

HRID 73750 반응식
[OH-].[Na+].[OH:3][C@@H:4]1[CH2:8][CH2:7][N:6]([C:9]2[C:18]([C:19]3[N:23]([CH:24]4[CH2:29][CH2:28][CH2:27][CH2:26][O:25]4)[N:22]=[CH:21][CH:20]=3)=[CH:17][C:12]([C:13]([O:15]C)=[O:14])=[CH:11][N:10]=2)[CH2:5]1>CO>[OH:3][C@@H:4]1[CH2:8][CH2:7][N:6]([C:9]2[C:18]([C:19]3[N:23]([CH:24]4[CH2:29][CH2:28][CH2:27][CH2:26][O:25]4)[N:22]=[CH:21][CH:20]=3)=[CH:17][C:12]([C:13]([OH:15])=[O:14])=[CH:11][N:10]=2)[CH2:5]1

참가 물질

4

반응물 2

HCID 14798Sodium HydroxideHCID 72546086methyl 6-((R)-3-hydroxypyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinate

생성물 1

HCID 725460876-((R)-3-hydroxypyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinic acid

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

Aq. NaOH (180 mL of 2.6 M) was added to a solution of methyl 6-((R)-3-hydroxypyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinate (Stage 9.5, 111 g, 299 mmol) in MeOH (270 mL) and the RM was stirred at RT for 14 h. The MeOH was evaporated off under reduced pressure and the aq. residue was treated with brine (90 mL), extracted with MeTHF twice (540 mL+360 mL) and the combined organic layers were washed with water (90 mL). MeTHF was added to the combined aq. layers, the biphasic mixture was cooled to 0° C. and acidified (pH=4-4.5) with aq. HCl solution (18%) and extracted with MeTHF. The combined organic extracts were washed with brine and the solvent was evaporated off under reduced pressure to give a residue which was recrystallized from a EtOAc/TBME (1:1) to afford the title compound as a white solid. HPLC (Condition 7) tR=4.74 min, LC-MS (Condition 8) tR=3.37 min, m/z=359.0 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.44 (br. s, 2H), 1.51 (d, J=11.54 Hz, 2H), 1.64-1.86 (m, 4H), 1.90 (br. s, 1H), 2.31 (d, J=9.29 Hz, 1H), 2.77 (br. s, 1H), 3.10 (br. s, 1H), 3.21 (d, J=8.78 Hz, 2H), 3.27-3.51 (m, 4H), 3.87 (d, J=11.54 Hz, 1H), 4.16 (br. s, 1H), 4.75-4.93 (m, 1H), 5.04 (br. s, 1H), 6.35 (d, J=17.32 Hz, 1H), 7.51-7.64 (m, 1H), 7.64-7.82 (m, 1H), 8.67 (d, J=2.26 Hz, 1H), 12.58 (br. s, 1H).

후처리

  1. customThe MeOH was evaporated off under reduced pressure
  2. additionthe aq. residue was treated with brine (90 mL)
  3. extractionextracted with MeTHF twice (540 mL+360 mL)
  4. washthe combined organic layers were washed with water (90 mL)
  5. additionMeTHF was added to the combined aq. layers
  6. temperaturethe biphasic mixture was cooled to 0° C.
  7. extractionextracted with MeTHF
  8. washThe combined organic extracts were washed with brine
  9. customthe solvent was evaporated off under reduced pressure
  10. customto give a residue which
  11. customwas recrystallized from a EtOAc/TBME (1:1)

출처 및 근거

ORD 기록
ord-8b6a364f7a3740beb3061375b14d4bef
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08829195B2

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