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4-Methylmorpholine → [1-(4-Cyano-2-{5-[4-(6-{2-[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2,2-dimethyl-propyl]-carbamic acid methyl ester

HRID 2392451
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HRID 2392451 반응식
[CH3:1][O:2][C:3]([NH:5][CH:6]([C:10]([CH3:13])([CH3:12])[CH3:11])[C:7]([OH:9])=O)=[O:4].C1C=CC2N(O)N=NC=2C=1.Cl.Cl.Cl.[CH3:27][O:28][C:29](=[O:77])[NH:30][CH:31]([C:35]([N:37]1[CH:43]([C:44]2[NH:45][C:46]([C:49]3[CH:58]=[CH:57][C:56]4[C:51](=[CH:52][CH:53]=[C:54]([C:59]5[CH:64]=[CH:63][C:62]([C:65]6[NH:66][C:67]([CH:70]7[CH2:74][CH:73]([C:75]#[N:76])[CH2:72][NH:71]7)=[N:68][CH:69]=6)=[CH:61][CH:60]=5)[CH:55]=4)[CH:50]=3)=[CH:47][N:48]=2)[CH2:42][C:39]2([CH2:41][CH2:40]2)[CH2:38]1)=[O:36])[CH:32]([CH3:34])[CH3:33].CN1CCOCC1>CN(C=O)C.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:4])[NH:5][CH:6]([C:7]([N:71]1[CH2:72][CH:73]([C:75]#[N:76])[CH2:74][CH:70]1[C:67]1[NH:66][C:65]([C:62]2[CH:63]=[CH:64][C:59]([C:54]3[CH:53]=[CH:52][C:51]4[C:56](=[CH:57][CH:58]=[C:49]([C:46]5[NH:45][C:44]([CH:43]6[CH2:42][C:39]7([CH2:41][CH2:40]7)[CH2:38][N:37]6[C:35](=[O:36])[CH:31]([NH:30][C:29]([O:28][CH3:27])=[O:77])[CH:32]([CH3:34])[CH3:33])=[N:48][CH:47]=5)[CH:50]=4)[CH:55]=3)=[CH:60][CH:61]=2)=[CH:69][N:68]=1)=[O:9])[C:10]([CH3:13])([CH3:12])[CH3:11]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 103301332-((Methoxycarbonyl)amino)-3,3-dimethylbutanoic acidHCID 66620685(1-{6-[5-(6-{4-[2-(4-Cyano-pyrrolidin-2-yl)-3H-imidazol-4-yl]-phenyl]-naphthalen-2-yl)-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester tris-hydrochloride

생성물 1

HCID 66632855
[1-(4-Cyano-2-{5-[4-(6-{2-[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2,2-dimethyl-propyl]-carbamic acid methyl ester
수율 45.1%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

2-Methoxycarbonylamino-3,3-dimethyl-butyric acid (43 mg, 0.227 mmol) EDC-HCl (44 mg, 0.227 mmol) and HOBt (32 mg, 0.237 mmol) were combined in DMF (2 mL) and stirred for 20 min at RT. (1-{6-[5-(6-{4-[2-(4-Cyano-pyrrolidin-2-yl)-3H-imidazol-4-yl]-phenyl]-naphthalen-2-yl)-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester tris-hydrochloride (150 mg, 0.189 mg) was added, the reaction mixture was cooled to 0° C. and NMM (0.104 mL, 0.947 mmol) was added dropwise. After 20, the reaction mixture was warmed to RT. 30 min later, the mixture was diluted with EtOAc and washed with NaHCO3, then brine. The organic phase was dried over MgSO4, then filtered and concentrated. The resulting residue was purified by HPLC to afford the title compound (73 mg, 45%). MS (ESI) m/z 854 [M+H]+.

후처리

  1. temperaturethe reaction mixture was cooled to 0° C.
  2. temperatureAfter 20, the reaction mixture was warmed to RT
  3. washwashed with NaHCO3
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by HPLC

출처 및 근거

ORD 기록
ord-b53107265cb445f9aa09d5a51f21401a
출처 데이터셋
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08273341B2

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