Dichloromethane → HCID 76604934, 화합물

HRID 1893680

반응식

HRID 1893680 반응식
C(OC(=O)[NH:7][CH:8]([C:13]([N:15]1[CH2:19][CH:18]([O:20][C:21]2[C:30]3[C:25](=C(Cl)[CH:27]=[CH:28][CH:29]=3)[N:24]=[C:23]([O:32][CH2:33][CH:34]([O:37][CH3:38])[O:35][CH3:36])[CH:22]=2)[CH2:17][CH:16]1[C:39](=[O:57])[NH:40][C:41]1([C:46]([NH:48][S:49]([O:52][C:53]2([CH3:56])[CH2:55][CH2:54]2)(=[O:51])=[O:50])=[O:47])[CH2:43][CH:42]1[CH2:44][CH3:45])=[O:14])[C:9]([CH3:12])([CH3:11])[CH3:10])(C)(C)C.C(O)(C(F)(F)F)=O.[F:66][C:67]([F:85])([F:84])[C:68]([O:71][C:72](=[O:83])OC1C=CC([N+]([O-])=O)=CC=1)([CH3:70])[CH3:69].C(N(C(C)C)CC)(C)C.[CH2:95]([Cl:97])Cl>CO>[F:85][C:67]([F:66])([F:84])[C:68]([O:71][C:72](=[O:83])[NH:7][CH:8]([C:13]([N:15]1[CH2:19][CH:18]([O:20][C:21]2[C:30]3[C:25](=[C:95]([Cl:97])[CH:27]=[CH:28][CH:29]=3)[N:24]=[C:23]([O:32][CH2:33][CH:34]([O:35][CH3:36])[O:37][CH3:38])[CH:22]=2)[CH2:17][CH:16]1[C:39](=[O:57])[NH:40][C:41]1([C:46]([NH:48][S:49]([O:52][C:53]2([CH3:56])[CH2:54][CH2:55]2)(=[O:50])=[O:51])=[O:47])[CH2:43][CH:42]1[CH2:44][CH3:45])=[O:14])[C:9]([CH3:10])([CH3:11])[CH3:12])([CH3:69])[CH3:70]

참가 물질

7

반응물 5

HCID 6344Dichloromethane2회HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 577851834-Nitrophenyl 1,1,1-Trifluoro-2-Methylpropan-2-yl-carbonateHCID 76605053HCID 76605053, 화합물

생성물 1

HCID 76604934HCID 76604934, 화합물수율 47%

시약·촉매·용매 1

HCID 887Methanol용매2회

실험 절차

(1-{4-[8-chloro-2-(2,2-dimethoxy-ethoxy)-quinolin-4-yloxy]-2-[2-ethyl-1-(1-methyl-cyclopropoxysulfonylaminocarbonyl)-cyclopropylcarbamoyl]-pyrrolidine-1-carbonyl}-2,2-dimethyl-propyl)-carbamic acid tert-butyl ester (444 mg, 0.520 mmol) was dissolved in CH2Cl2 (2.6 mL) and MeOH (0.21 mL, 5.20 mmol), and treated with TFA (2.6 mL). After stirring for 25 min at room temperature, MeOH (7 mL) was added and the solvents were removed in vacuo. The crude mixture was partitioned with saturated NaHCO3 and DCM. The layers were separated and the organic layer was dried over Na2SO4 and concentrated. The resultant residue was dissolved in DCM (5.2 mL) to which carbonic acid 4-nitro-phenyl ester 2,2,2-trifluoro-1,1-dimethyl-ethyl ester (183 mg, 0.624 mmol) and diisopropylethylamine (362 μL, 2.08 mmol) were added sequentially. After stirring for 24 h at 35° C., the reaction was purified by column chromatography on silica (3-7% MeOH/DCM) to provide (1-{4-[8-chloro-2-(2,2-dimethoxy-ethoxy)-quinolin-4-yloxy]-2-[2-ethyl-1-(1-methyl-cyclopropoxysulfonylaminocarbonyl)-cyclopropylcarbamoyl]-pyrrolidine-1-carbonyl}-2,2-dimethyl-propyl)-carbamic acid 2,2,2-trifluoro-1,1-dimethyl-ethyl ester (222 mg, 47% yield). LCMS found 908.0 [M+H]+.

후처리

  1. customthe solvents were removed in vacuo
  2. customThe crude mixture was partitioned with saturated NaHCO3 and DCM
  3. customThe layers were separated
  4. dry with materialthe organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. additionwere added sequentially
  7. stirringAfter stirring for 24 h at 35° C.
  8. customthe reaction was purified by column chromatography on silica (3-7% MeOH/DCM)

출처 및 근거

ORD 기록
ord-6c9e51470b9342ec910f1bbf0d91b3b5
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08513186B2

연결된 노트

불러오는 중…