Ethanol → 2-(4-((2-Amino-4-methyl-6-(pentylamino)pyrimidin-5-yl)methyl)phenyl)acetic acid
Reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH2:9][C:10]2[CH:15]=[CH:14][C:13](CC#N)=[CH:12][CH:11]=2)=[C:4]([NH:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[N:3]=1.[OH-:25].[K+].[CH2:27]([OH:29])[CH3:28]>>[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:28][C:27]([OH:25])=[O:29])=[CH:12][CH:11]=2)=[C:4]([NH:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[N:3]=1Participants
Conditions
- Temperature
- 80 °C
Procedure
A mixture of the product from step (iv) (51.7 g) and 5 M KOH (517 g) in ethanol (204 g) was heated at 80° C. for 4 hours. After the solvent was evaporated under reduced pressure, the residue was diluted with water (259 mL) and washed with t-butyl methyl ether (390 g) at 25° C. The solution was cooled to 5° C. and the pH of the solution was adjusted to pH 5 with conc. HCl. The resulting precipitate was collected by filtration, washed with a solution of water (200 mL) and MeCN (200 g) and dried to afford the subtitle compound as a solid, 57.0 g; containing 4.5% weight of water; 1H NMR DMSO-d6: 7.12 (d, 2H), 7.02 (d, 2H), 6.32 (t, 1H), 5.94 (brs, 2H), 3.71 (s, 2H), 3.46 (s, 2H), 3.27-3.23 (m, 2H), 2.00 (s, 3H), 1.48-1.41 (m, 2H), 1.27-1.21 (m, 2H), 1.18-1.13 (m, 2H), 0.82 (t, 3H).
Workup
- customAfter the solvent was evaporated under reduced pressure
- additionthe residue was diluted with water (259 mL)
- washwashed with t-butyl methyl ether (390 g) at 25° C
- temperatureThe solution was cooled to 5° C.
- filtrationThe resulting precipitate was collected by filtration
- washwashed with a solution of water (200 mL) and MeCN (200 g)
- customdried
Sources & evidence
- ORD record
- ord-5f0af5ca273e437fa7a7a8b3d7684d94
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08476288B2
Reaction notes
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