Trifluoroacetic acid → Trifluoroacetic acid

HRID 338640노트

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HRID 338640 반응식
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([CH3:56])([CH3:55])[C@H:13]3[C@:26]([CH3:29])([CH2:27][CH:28]=2)[C@@H:25]2[C@:16]([CH3:54])([C@@:17]4([CH3:53])[C@H:22]([CH2:23][CH2:24]2)[C@H:21]2[C@H:30]([C:33]([CH3:35])=[CH2:34])[CH2:31][CH2:32][C@:20]2([NH:36][CH2:37][CH2:38][N:39]2[CH2:44][C@@H:43]5[CH2:45][C@H:40]2[CH2:41][N:42]5C(OC(C)(C)C)=O)[CH2:19][CH2:18]4)[CH2:15][CH2:14]3)=[CH:7][CH:6]=1)=[O:4].[C:57]([OH:63])([C:59]([F:62])([F:61])[F:60])=[O:58]>C(Cl)Cl>[C@H:40]12[CH2:45][C@H:43]([NH:42][CH2:41]1)[CH2:44][N:39]2[CH2:38][CH2:37][NH:36][C@:20]12[CH2:32][CH2:31][C@@H:30]([C:33]([CH3:35])=[CH2:34])[C@@H:21]1[C@@H:22]1[C@@:17]([CH3:53])([CH2:18][CH2:19]2)[C@@:16]2([CH3:54])[C@@H:25]([C@:26]3([CH3:29])[C@@H:13]([CH2:14][CH2:15]2)[C:12]([CH3:55])([CH3:56])[C:11]([C:8]2[CH:9]=[CH:10][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][CH:7]=2)=[CH:28][CH2:27]3)[CH2:24][CH2:23]1.[C:57]([OH:63])([C:59]([F:62])([F:61])[F:60])=[O:58]

참가 물질

5

반응물 2

HCID 6422Trifluoroacetic acidHCID 86701804HCID 86701804, 화합물

생성물 2

HCID 6422Trifluoroacetic acid수율 121%HCID 86701803HCID 86701803, 화합물

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of (1S,4S)-tert-butyl 5-(2-(((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(4-(methoxycarbonyl)phenyl)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-3a-yl)amino)ethyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (419 mg, 0.545 mmol) in DCM (10 mL) was added TFA (2 mL, 26.0 mmol) and the mixture was stirred at rt for 3 h. The reaction mixture was concentrated and dark brown viscous oil was dried to remove all TFA. The material was purified by reverse phase HPLC using HPLC method 6 and dried under vacuum to give methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate, 3 TFA (75.2 mg, 12.28% yield) as a light brown solid. LC/MS: m/e 668.7 (M+H)+, 2.36 min (method 3). 1H NMR (400 MHz, CHLOROFORM-d) δ 9.77 (br. s., 1H), 9.49 (br. s., 1H), 7.92 (d, J=8.1 Hz, 2H), 7.19 (d, J=8.1 Hz, 2H), 5.28 (d, J=4.4 Hz, 1H), 4.76 (br. s., 1H), 4.69 (br. s., 1H), 4.31 (br. s., 1H), 3.96 (br. s., 1H), 3.90 (s, 3H), 3.66 (br. s., 1H), 3.40-3.10 (m, 5H), 3.09-2.89 (m, 2H), 2.81 (br. s., 1H), 2.23-2.06 (m, 4H), 2.05-1.91 (m, 3H), 1.85 (br. s., 1H), 1.78-1.73 (m, 1H), 1.69 (br. s., 3H), 1.65 (br. s., 1H), 1.62-1.30 (m, 11H), 1.26-1.17 (m, 2H), 1.11 (br. s., 3H), 1.05 (br. s., 3H), 0.99 (br. s., 3H), 0.93 (br. s., 6H). 13C NMR (101 MHz, CHLOROFORM-d) 167.2, 148.5, 147.1, 146.2, 130.0, 128.5, 127.9, 123.8, 114.8, 111.6, 77.24-77.18, 71.3, 65.8, 60.9, 57.7, 54.4, 52.7, 52.0, 49.2, 48.7, 48.62-48.49, 46.3, 45.0, 42.0, 41.6, 40.6, 37.4, 37.0, 36.2, 33.6, 32.5, 29.4, 28.0, 27.3, 25.8, 25.0, 20.9, 20.8, 19.5, 19.1, 16.3, 15.9, 15.2, 14.4.

후처리

  1. concentrationThe reaction mixture was concentrated
  2. customdark brown viscous oil was dried
  3. customto remove all TFA
  4. customThe material was purified by reverse phase
  5. customdried under vacuum

출처 및 근거

ORD 기록
ord-49d4196d23a24069a021a516039f0981
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889854B2

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