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 625509ノート

反応式

HRID 625509 の反応式
[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

参加物

7

反応物 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

生成物 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)isophthalamide収率 37%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-4a54ffe5df9944b5a58e5e3d02d9ea95
出典データセット
uspto-grants-2016_04
特許番号
US09301951B2

反応ノート

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