Methanol → 2-[4-[[2-(5-chloro-2-thienyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]amino]phenyl]acetic acid

HRID 1508716Notes

Reaction equation

HRID 1508716 reaction equation
C(OC[C:6]1[CH:11]=[C:10]([NH:12][C:13]2[C:18]([CH2:19][CH3:20])=[C:17]([CH3:21])[N:16]=[C:15]([C:22]3[S:23][C:24]([Cl:27])=[CH:25][CH:26]=3)[N:14]=2)[CH:9]=[CH:8][C:7]=1B1OC(C)(C)C(C)(C)O1)(=O)C.[OH-:37].[Li+].[CH2:39]1[CH2:43][O:42]CC1.CO>O>[Cl:27][C:24]1[S:23][C:22]([C:15]2[N:14]=[C:13]([NH:12][C:10]3[CH:11]=[CH:6][C:7]([CH2:39][C:43]([OH:37])=[O:42])=[CH:8][CH:9]=3)[C:18]3[CH2:19][CH2:20][CH2:21][C:17]=3[N:16]=2)=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 90112797[5-[[2-(5-Chloro-2-thienyl)-5-ethyl-6-methyl-pyrimidin-4-yl]amino]-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl acetate

Product 1

HCID 742209102-[4-[[2-(5-chloro-2-thienyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]amino]phenyl]acetic acidYield 68%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 18-mL vial was charged with [5-[[2-(5-chloro-2-thienyl)-5-ethyl-6-methyl-pyrimidin-4-yl]amino]-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl acetate (8.6 mg, 0.016 mmol) and lithium hydroxide (10 mg, 0.23 mmol). THF (1 ml), MeOH (0.2 ml) and water (0.2 ml) was added to the vial. The resulting mixture was stirred at rt overnight. Then the volatile material was removed. The residue was treated with THF (0.5 ml) and 2N HCl aq. (0.5 ml) for 1 hr. The mixture was neutralized by addition of NaHCO3 aq. to pH=7. Then the mixture was extracted with ethyl acetate (3×2 ml). The ethyl acetate layers were combined and solvent was removed to dryness and the residue was purified by chromatography on silica gel using DCM followed by 0.4% MeOH in DCM as eluent to afford 2-[4-[[2-(5-chloro-2-thienyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]amino]phenyl]acetic acid (4.2 mg, 68% yield). MW=385.68. 1H NMR (CDCl3, 400 MHz) δ 7.98 (s, 1H), 7.75 (d, J=8.0 Hz, 1H), 7.67 (d, J=4.0 Hz, 1H), 7.48 (d, J=8.0 Hz, 1H), 6.95 (d, J=4.0 Hz, 1H), 6.68 (brs, 1H), 5.18 (s, 2H), 2.68 (q, J=8.0 Hz, 2H), 2.51 (s, 3H), 1.27 (t, J=8.0 Hz, 3H).

Workup

  1. customThen the volatile material was removed
  2. additionThe residue was treated with THF (0.5 ml) and 2N HCl aq. (0.5 ml) for 1 hr
  3. additionThe mixture was neutralized by addition of NaHCO3 aq. to pH=7
  4. extractionThen the mixture was extracted with ethyl acetate (3×2 ml)
  5. customsolvent was removed to dryness
  6. customthe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-6a399855ebfd440495efc927e95eb56b
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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