Citric Acid → AZD 8055

HRID 218348Notes

Reaction equation

HRID 218348 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.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(Cl)Cl>C1COCC1.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

7

Reactant 4

HCID 311Citric AcidHCID 6344DichloromethaneHCID 14797Potassium HydroxideHCID 58015470HCID 58015470, compound

Product 1

HCID 25262965AZD 8055Yield 95.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Potassium hydroxide solution (1.7 mL, 3.10 mmol) was added to a solution of 5-{2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl}-2-methoxybenzyl pivalate (172 mg, 0.30 mmol) in THF (6.9 mL) and methanol (1.7 mL) at RT under an atmosphere of nitrogen. After 240 minutes, HPLC analysis showed complete disappearance of the starting material. The reaction was maintained at RT overnight (for convenience) and aqueous citric acid (20% w/v, 2 mL) was added followed by methylene chloride (15 mL). The upper aqueous layer was extracted with two further extractions of methylene chloride (2×15 mL) and the organic layers combined. Evaporation of the methylene chloride afforded (5-{2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl}-2-methoxyphenyl)methanol (6) as a yellow solid (133 mg).

Workup

  1. additionwas added
  2. extractionThe upper aqueous layer was extracted with two further extractions of methylene chloride (2×15 mL)
  3. customEvaporation of the methylene chloride

Sources & evidence

ORD record
ord-1e8fd2605e1a40998b3229de0c17020b
Source dataset
uspto-grants-2012_06
Patent number
US08198441B2

Reaction notes

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