Triethylamine → 2-[4-[4-(Methoxymethyl)-1-piperidyl]-5-phenyl-thieno[2,3-d]pyrimidin-2-yl]acetic acid

HRID 928617Notes

Reaction equation

HRID 928617 reaction equation
Cl[C:2]1[C:3]2[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:15][S:14][C:4]=2[N:5]=[C:6]([CH2:8][C:9]([O:11]CC)=[O:10])[N:7]=1.Cl.[CH3:24][O:25][CH2:26][CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.C(N(CC)CC)C>C(O)C>[CH3:24][O:25][CH2:26][CH:27]1[CH2:32][CH2:31][N:30]([C:2]2[C:3]3[C:16]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:15][S:14][C:4]=3[N:5]=[C:6]([CH2:8][C:9]([OH:11])=[O:10])[N:7]=2)[CH2:29][CH2:28]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 11595162(4-Chloro-5-phenylthieno[2,3-d]pyrimidin-2-yl)acetic acid ethyl esterHCID 172185994-(Methoxymethyl)piperidine hydrochloride

Product 1

HCID 895793932-[4-[4-(Methoxymethyl)-1-piperidyl]-5-phenyl-thieno[2,3-d]pyrimidin-2-yl]acetic acidYield 94.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
65 °C

Procedure

Ethyl 2-(4-chloro-5-phenyl-thieno[2,3-d]pyrimidin-2-yl)acetate (100 mg, 0.285 mmol), 4-(methoxymethyl)piperidine hydrochloride (52 mg, 0.314 mmol) and triethylamine (0.12 mL, 0.85 mmol) were dissolved in ethanol (4 mL) and heated to 65° C. for 6 hrs. The reaction was then heated to 150° C. in a microwave for 10 min. The reaction was poured over ice and extracted with DCM. The extracts were combined and concentrated in vacuo. The residue was dissolved in non-dry THF (2 mL) and lithium hydroxide monohydrate (48 mg) was added. The reaction was stirred at room temperature overnight then another portion of lithium hydroxide monohydrate was added (10 mg) and the reaction stirred for a further 2 hrs. The reaction mixture was purified on an Isolute NH2 SPE column (eluting ammonia in methanol) to give 2-[4-[4-(methoxymethyl)-1-piperidyl]-5-phenyl-thieno[2,3-d]pyrimidin-2-yl]acetic acid (107 mg).

Workup

  1. temperatureThe reaction was then heated to 150° C. in a microwave for 10 min
  2. additionThe reaction was poured over ice
  3. extractionextracted with DCM
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in non-dry THF (2 mL)
  6. additionlithium hydroxide monohydrate (48 mg) was added
  7. additionanother portion of lithium hydroxide monohydrate was added (10 mg)
  8. stirringthe reaction stirred for a further 2 hrs
  9. customThe reaction mixture was purified on an Isolute NH2 SPE column (eluting ammonia in methanol)

Sources & evidence

ORD record
ord-bd8a3e4f048947529a473c67e94be91e
Source dataset
uspto-grants-2016_03
Patent number
US09290511B2

Reaction notes

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