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

HRID 1508716ノート

反応式

HRID 1508716 の反応式
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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-6a399855ebfd440495efc927e95eb56b
出典データセット
uspto-grants-2015_12
特許番号
US09221843B2

反応ノート

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