2,2-Difluoro-1,3-benzodioxole-5-carbonyl chloride → 2,2-Difluoro-benzo[1,3]dioxole-5-carboxylic Acid [4-((S)-2-amino-propoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-amide

HRID 1685944노트

반응식

HRID 1685944 반응식
[NH2:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][CH2:7][C@@H:8]([NH:10]C(=O)OC(C)(C)C)[CH3:9])=[C:4]([C:20]2[N:24]([CH3:25])[N:23]=[CH:22][CH:21]=2)[CH:3]=1.[F:26][C:27]1([F:39])[O:31][C:30]2[CH:32]=[CH:33][C:34]([C:36](Cl)=[O:37])=[CH:35][C:29]=2[O:28]1>C(Cl)Cl>[NH2:10][C@@H:8]([CH3:9])[CH2:7][O:6][C:5]1[CH:18]=[CH:19][C:2]([NH:1][C:36]([C:34]2[CH:33]=[CH:32][C:30]3[O:31][C:27]([F:39])([F:26])[O:28][C:29]=3[CH:35]=2)=[O:37])=[CH:3][C:4]=1[C:20]1[N:24]([CH3:25])[N:23]=[CH:22][CH:21]=1

참가 물질

4

반응물 2

HCID 27740642,2-Difluoro-1,3-benzodioxole-5-carbonyl chlorideHCID 86633183tert-butyl(S)-1-(4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)propan-2-ylcarbamate

생성물 1

HCID 578145452,2-Difluoro-benzo[1,3]dioxole-5-carboxylic Acid [4-((S)-2-amino-propoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-amide

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
40 °C

실험 절차

To a solution of tert-butyl (S)-1-(4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)propan-2-ylcarbamate (40.0 mg, 115 μmol) in DCM was added 2,2-difluorobenzo[d][1,3]dioxole-5-carbonyl chloride (28.0 mg, 127 μmol) followed by TEA (32.2 μl, 231 μmol). The reaction was mixed in a rotary shaker at 25° C. for 1 hour then quenched with MeOH (100 μl). After mixing for 20 minutes TFA (400 μl) was added and the resulting mixture was heated to 40° C. and mixed for 1 hour. The organic solvent was removed under vacuum; the crude residue was dissolved in acetonitrile (0.5 mL), neutralized with saturated bicarbonate and subjected to purification by preparative LCMS. The proper fractions were pooled, frozen and lyophilized to afford the title compound as an off white solid (16.7% yield). LCMS m/z=431.3 (M+H); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.16 (d, J=6.82 Hz, 3 H), 3.48-3.58 (m, 1 H), 3.71 (s, 3 H), 3.99-4.08 (m, 2 H), 6.36 (d, J=1.77 Hz, 1 H), 7.25 (d, J=9.09 Hz, 1 H), 7.50 (d, J=1.77 Hz, 1 H), 7.60 (d, J=8.59 Hz, 1 H), 7.71 (d, J=2.53 Hz, 2 H), 7.82-7.91 (m, 2 H), 10.35 (s, 1 H).

후처리

  1. additionThe reaction was mixed in a rotary shaker at 25° C. for 1 hour
  2. customthen quenched with MeOH (100 μl)
  3. additionAfter mixing for 20 minutes TFA (400 μl)
  4. additionwas added
  5. additionmixed for 1 hour
  6. customThe organic solvent was removed under vacuum
  7. dissolutionthe crude residue was dissolved in acetonitrile (0.5 mL)
  8. customsubjected to purification by preparative LCMS
  9. temperaturefrozen

출처 및 근거

ORD 기록
ord-8e91c4c921db42a489d42b306f4e8e55
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08148417B2

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