Acetic Acid → (S)-N1-Methyl-N1-(23-methyl-2,5,8,11,14,17,20-heptaoxa-23-azapentacosan-25-yl)-N3-(4-(piperidin-1-yl)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenyl)isophthalamide

HRID 1408252노트

반응식

HRID 1408252 반응식
[C:1]([BH3-])#[N:2].[Na+].[CH3:5][N:6]([CH2:49][CH:50]=O)[C:7](=[O:48])[C:8]1[CH:47]=[CH:46][CH:45]=[C:10]([C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)=[CH:16][C:15]=2[C:26]2[CH:31]=[C:30]([C:32](=[O:44])[NH:33][C@@H:34]3[C:43]4[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=4)[CH2:37][CH2:36][CH2:35]3)[CH:29]=[CH:28][N:27]=2)=[O:12])[CH:9]=1.CN[CH2:54][CH2:55][O:56][CH2:57][CH2:58][O:59][CH2:60][CH2:61][O:62][CH2:63][CH2:64][O:65][CH2:66][CH2:67][O:68][CH2:69][CH2:70][O:71][CH2:72][CH2:73][O:74][CH3:75].C(O)(=O)C>C(O)C.C(OCC)(=O)C>[CH3:5][N:6]([CH2:49][CH2:50][N:2]([CH3:1])[CH2:54][CH2:55][O:56][CH2:57][CH2:58][O:59][CH2:60][CH2:61][O:62][CH2:63][CH2:64][O:65][CH2:66][CH2:67][O:68][CH2:69][CH2:70][O:71][CH2:72][CH2:73][O:74][CH3:75])[C:7](=[O:48])[C:8]1[CH:47]=[CH:46][CH:45]=[C:10]([C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]3)=[CH:16][C:15]=2[C:26]2[CH:31]=[C:30]([C:32](=[O:44])[NH:33][C@@H:34]3[C:43]4[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=4)[CH2:37][CH2:36][CH2:35]3)[CH:29]=[CH:28][N:27]=2)=[O:12])[CH:9]=1

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 86705967(S)-N1-methyl-N1-(2-oxoethyl)-N3-(4-(piperidin-1-yl)-2-(4-((1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyridin-2-yl)phenyl)isophthalamideHCID 86705991mPEG7-NHMe

생성물 1

HCID 86706000(S)-N1-Methyl-N1-(23-methyl-2,5,8,11,14,17,20-heptaoxa-23-azapentacosan-25-yl)-N3-(4-(piperidin-1-yl)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenyl)isophthalamide수율 37%

시약·촉매·용매 2

HCID 702Ethanol용매HCID 8857Ethyl Acetate용매

실험 절차

Sodium cyanoborohydride (0.75 g, 11.9 mmol) was added portionwise to (S)—N1-methyl-N1-(2-oxoethyl)-N3-(4-(piperidin-1-yl)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenyl)isophthalamide 187a (1.5 g, 2.38 mmol), N-methyl-2,5,8,11,14,17,20-heptaoxadocosan-22-amine 135c.1 (2.52 g, 7.14 mmol) and acetic acid (0.41 mL, 7.14 mmol) in ethanol (15 mL) and the mixture stirred overnight at room temperature. The reaction was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate and brine, dried (MgSO4). The residue was purified by PTLC (10% MeOH/20% ethyl acetate/dichloromethane) to give product as an orange oil (0.85 g, 37%); MS (ES, m/z): 969 [M+H]+; NMR (400 MHz, CDCl3, ppm): δ 12.8 (s, 1H); 8.80 (s, 1H); 8.55 (d, J=8.8 Hz, 1H); 8.10 (s, 1H); 7.98-8.02 (m, 2H); 7.47-7.55 (m, 3H); 7.06-7.24 (m, 5H); 6.69 (m, 1H); 5.41 (m, 1H).

후처리

  1. washwashed with saturated aqueous sodium bicarbonate and brine
  2. dry with materialdried (MgSO4)
  3. customThe residue was purified by PTLC (10% MeOH/20% ethyl acetate/dichloromethane)

출처 및 근거

ORD 기록
ord-d22179a715b54ffd973b853dd7a6472e
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08916569B2

반응 노트

불러오는 중…