Potassium Hydroxide → AZD 8055

HRID 218349Notes

Reaction equation

HRID 218349 reaction equation
[OH-].[K+].C([O:9][CH2:10][C:11]1[CH:16]=[C:15]([C:17]2[CH:18]=[CH:19][C:20]3[C:25]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][C@@H:27]4[CH3:32])=[N:24][C:23]([N:33]4[CH2:38][CH2:37][O:36][CH2:35][C@@H:34]4[CH3:39])=[N:22][C:21]=3[N:40]=2)[CH:14]=[CH:13][C:12]=1[O:41][CH3:42])(=O)C(C)(C)C>CO>[CH3:39][C@H:34]1[CH2:35][O:36][CH2:37][CH2:38][N:33]1[C:23]1[N:24]=[C:25]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][C@@H:27]2[CH3:32])[C:20]2[CH:19]=[CH:18][C:17]([C:15]3[CH:14]=[CH:13][C:12]([O:41][CH3:42])=[C:11]([CH2:10][OH:9])[CH:16]=3)=[N:40][C:21]=2[N:22]=1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 58015470HCID 58015470, compound

Product 1

HCID 25262965AZD 8055

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Potassium hydroxide solution (9.96 mL, 133.20 mmol) was added over 30 minutes to a solution of 5-{2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl}-2-methoxybenzyl pivalate prepared by the alternate method (25.16 g, 0.30 mmol) in methanol (244 mL) at 50° C. under an atmosphere of nitrogen. After 120 minutes at 50° C., HPLC analysis showed complete disappearance of the starting material. Seed crystals of the desired compound were then added (122 mg, 257 μmol) and the reaction was maintained at 50° C. for 2 hours to establish crystallisation of the desired product. Water, (244 mL) is then added over 15 minutes maintaining a reaction temperature of 50° C. The reaction mixture is then cooled to 20° C. and the resulting yellow solid isolated by filtration. The yellow solid was washed with water (3×97 mL) and dried initially in air and then in vacuo at 45° C. to give (5-{2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl}-2-methoxyphenyl)methanol (6) as a yellow solid (19.33 g).

Sources & evidence

ORD record
ord-968c7b60f56e4bad92e4a30e292f1e91
Source dataset
uspto-grants-2012_06
Patent number
US08198441B2

Reaction notes

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