Diethyl Ether → 4-(Azetidin-1-ylmethyl)piperidine-1-carboxylic acid {4-[2-fluoro-4-(3-phenylacetylureido)phenoxy]pyridin-2-yl}amide

HRID 492978노트

반응식

HRID 492978 반응식
[NH2:1][C:2]1[CH:28]=[CH:27][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][CH:19]([CH2:22][N:23]4[CH2:26][CH2:25][CH2:24]4)[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[C:4]([F:29])[CH:3]=1.[C:30]1([CH2:36][C:37]([N:39]=[C:40]=[O:41])=[O:38])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(OCC)C>CN(C)C=O.CCCCCC>[F:29][C:4]1[CH:3]=[C:2]([NH:1][C:40]([NH:39][C:37](=[O:38])[CH2:36][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[O:41])[CH:28]=[CH:27][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]2[CH2:21][CH2:20][CH:19]([CH2:22][N:23]3[CH2:24][CH2:25][CH2:26]3)[CH2:18][CH2:17]2)=[O:15])[CH:8]=1

참가 물질

6

반응물 3

HCID 3283Diethyl EtherHCID 12259960Phenylacetyl isocyanateHCID 866021764-(Azetidin-1-ylmethyl)piperidine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide

생성물 1

HCID 576775254-(Azetidin-1-ylmethyl)piperidine-1-carboxylic acid {4-[2-fluoro-4-(3-phenylacetylureido)phenoxy]pyridin-2-yl}amide

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8058Hexane용매2회

실험 절차

To a solution of 4-(azetidin-1-ylmethyl)piperidine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide (30 mg) in N,N-dimethylformamide (1 ml) was added a solution of 0.25 M 2-phenylacetyl isocyanate in hexane (0.901 ml) under a nitrogen atmosphere, followed by stirring for 1 hr. The reaction mixture was partitioned between ethyl acetate (100 ml) and a saturated aqueous solution of sodium hydrogencarbonate (50 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (50 ml), water (50 ml), brine (50 ml) and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=9:1). Fractions containing the target compound were concentrated to give a residue, to which were added diethyl ether (1.5 ml) and hexane (3 ml) to suspend. The solid was filtered off and dried under aeration to provide the titled compound (14.0 mg) as white powder.

후처리

  1. customThe reaction mixture was partitioned between ethyl acetate (100 ml)
  2. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (50 ml), water (50 ml), brine (50 ml)
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated
  5. customto give a residue, which
  6. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent
  7. additionFractions containing the target compound
  8. concentrationwere concentrated
  9. customto give a residue
  10. filtrationThe solid was filtered off
  11. customdried under aeration

출처 및 근거

ORD 기록
ord-35345f7fd0ea43d0ada3d2c6cf6bbcd7
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07531532B2

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