3-(p-Tolyl)acrylic acid → 5-[(R)-2-(2-{4-[4-(2-amino-2-methyl-propoxy)-phenylamino]-phenyl}-ethylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one 4-methyl-cinnamate

HRID 1437133Notes

Reaction equation

HRID 1437133 reaction equation
[NH2:1][C:2]([CH3:37])([CH3:36])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][NH:20][CH2:21][C@@H:22]([C:24]3[CH:33]=[CH:32][C:31]([OH:34])=[C:30]4[C:25]=3[CH:26]=[CH:27][C:28](=[O:35])[NH:29]4)[OH:23])=[CH:14][CH:13]=2)=[CH:7][CH:6]=1.[CH3:38][C:39]1[CH:49]=[CH:48][C:42]([CH:43]=[CH:44][C:45]([OH:47])=[O:46])=[CH:41][CH:40]=1>O1CCCC1.O>[CH3:38][C:39]1[CH:49]=[CH:48][C:42]([CH:43]=[CH:44][C:45]([OH:47])=[O:46])=[CH:41][CH:40]=1.[NH2:1][C:2]([CH3:37])([CH3:36])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]2[CH:13]=[CH:14][C:15]([CH2:18][CH2:19][NH:20][CH2:21][C@@H:22]([C:24]3[CH:33]=[CH:32][C:31]([OH:34])=[C:30]4[C:25]=3[CH:26]=[CH:27][C:28](=[O:35])[NH:29]4)[OH:23])=[CH:16][CH:17]=2)=[CH:7][CH:6]=1

Participants

5

Reactant 2

HCID 158353-(p-Tolyl)acrylic acidHCID 111693655-[(R)-2-(2-{4-[4-(2-amino-2-methyl-propoxy)-phenylamino]-phenyl}-ethylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one

Product 1

HCID 667958465-[(R)-2-(2-{4-[4-(2-amino-2-methyl-propoxy)-phenylamino]-phenyl}-ethylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one 4-methyl-cinnamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

5-[(R)-2-(2-{4-[4-(2-amino-2-methyl-propoxy)-phenylamino]-phenyl}-ethylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one (0.21 g) was dissolved in a mixture of tetrahydrofuran (1.2 mL) and water (1.2 mL). 4-methyl-cinnamic acid (0.07 g, predominantly trans ) was added to the stirred solution at room temperature and it dissolved. After approximately 10 min, crystallization occurred. The slurry was stirred overnight and filtered. The cake was washed with aqueous tetrahydrofuran (1:1 THF:water, 2×0.4 mL, 1×0.2 mL) to afford the title compound which was dried overnight under vacuum at 45° C. (yield: 0.207 g). 1H NMR (400 MHz, DMSO-d6; DMSO-d5 as reference at δ(ppm) 2.5). δ(ppm): 1.22 (6H) s; 2.30 (3H) s; 2.64 (2H) t J=6.6 Hz; 2.72-2.86 (4H) m; 3.74 (2H) s; 5.09 (1H) m; 6.43 (1H) d J=15.9 Hz; 6.49 (1H) d J=10.0 Hz; 6.86 (4H) m; 6.93-7.03 (5H) m; 7.06 (1H) d J=7.8 Hz; 7.17 (2H) d J=7.8 Hz; 7.34 (1H) d J=15.9 Hz; 7.45 (2H) d J=7.8 Hz; 7.75 (1H) s; 8.19 (1H) d J=10.0 Hz. The crystalline product was characterized by XRPD and DSC.

Workup

  1. dissolutionit dissolved
  2. customcrystallization
  3. filtrationfiltered
  4. washThe cake was washed with aqueous tetrahydrofuran (1:1 THF:water, 2×0.4 mL, 1×0.2 mL)

Sources & evidence

ORD record
ord-eccd7f9ae4ca48fd865e538fa1336e52
Source dataset
uspto-grants-2009_11
Patent number
US07622467B2

Reaction notes

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