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

HRID 1508716노트

반응식

HRID 1508716 반응식
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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 962Water용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-6a399855ebfd440495efc927e95eb56b
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221843B2

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