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 1670802Notes

Reaction equation

HRID 1670802 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-70a5d12113854bb69cba3a68646e6e8d
Source dataset
uspto-grants-2011_08
Patent number
US07994165B2

Reaction notes

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