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 625509Notes

Reaction equation

HRID 625509 reaction equation
[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

Participants

7

Reactant 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

Product 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)isophthalamideYield 37%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-4a54ffe5df9944b5a58e5e3d02d9ea95
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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