Diisopropylethylamine → Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(1-ethyl-1H-pyrazol-4-yl)nicotinate

HRID 2092820노트

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HRID 2092820 반응식
Cl[C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([C:14]2[CH:15]=[N:16][N:17]([CH2:19][CH3:20])[CH:18]=2)[N:3]=1.CCN(C(C)C)C(C)C.[NH2:30][C@@H:31]1[CH2:36][CH2:35][CH2:34][CH2:33][C@@H:32]1[NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41]>CN(C=O)C>[C:40]([O:39][C:38]([NH:37][C@H:32]1[CH2:33][CH2:34][CH2:35][CH2:36][C@H:31]1[NH:30][C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([C:14]2[CH:15]=[N:16][N:17]([CH2:19][CH3:20])[CH:18]=2)[N:3]=1)=[O:44])([CH3:43])([CH3:41])[CH3:42]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 58317713Methyl 6-chloro-4-cyano-2-(1-ethyl-1H-pyrazol-4-yl)nicotinate

생성물 1

HCID 67237978Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(1-ethyl-1H-pyrazol-4-yl)nicotinate수율 19.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
100 °C

실험 절차

To a solution of methyl 6-chloro-4-cyano-2-(1-ethyl-1H-pyrazol-4-yl)nicotinate (201 mg, 0.691 mmol) in DMF (1 mL) was added DIPEA (0.242 mL, 1.383 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (237 mg, 1.106 mmol). The reaction mixture was stirred at 100° C. overnight, after which the solvent was removed, and the resulting crude material was diluted in MeOH (5.0 mL) and purified via reverse phase preparative HPLC. The collected fractions were collected and ACN was removed via rotary evaporation. The resulting aq solution was neutralized with saturated aq NaHCO3 and washed with EtOAc (2×200 mL), dried over Na2SO4, and filtered. The organic phase was stripped to dryness via rotary evaporation to yield the title compound (62 mg, 19%). [M+H] calc'd for C24H32N6O4, 469. found, 469.

후처리

  1. customafter which the solvent was removed
  2. additionthe resulting crude material was diluted in MeOH (5.0 mL)
  3. custompurified via reverse phase preparative HPLC
  4. customThe collected fractions were collected
  5. customACN was removed via rotary evaporation
  6. washwashed with EtOAc (2×200 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customThe organic phase was stripped to dryness via rotary evaporation

출처 및 근거

ORD 기록
ord-74e5bfc791dd478398e8cde6a63ede1a
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08440689B2

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