Diisopropylethylamine → (3R)-1-[4-[5-[5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl]-1-methyl-1,2,4-triazol-3-yl]-1-piperidyl]-3-hydroxy-butan-1-one

HRID 1749687노트

반응식

HRID 1749687 반응식
[C:1]([C:5]1[O:9][C:8]([C:10]2[C:11]([NH2:28])=[N:12][CH:13]=[C:14]([C:16]3[N:20]([CH3:21])[N:19]=[C:18]([CH:22]4[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]4)[N:17]=3)[N:15]=2)=[N:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)C(C)C)C.[OH:38][C@H:39]([CH3:44])[CH2:40][C:41](O)=[O:42]>CN(C)C=O.C(#N)C>[NH2:28][C:11]1[N:12]=[CH:13][C:14]([C:16]2[N:20]([CH3:21])[N:19]=[C:18]([CH:22]3[CH2:23][CH2:24][N:25]([C:41](=[O:42])[CH2:40][C@H:39]([OH:38])[CH3:44])[CH2:26][CH2:27]3)[N:17]=2)=[N:15][C:10]=1[C:8]1[O:9][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[N:6][N:7]=1

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 921353-Hydroxybutanoic acid, (R)-HCID 867276583-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-(1-methyl-3-(piperidin-4-yl)-1H-1,2,4-triazol-5-yl)pyrazin-2-amine

생성물 1

HCID 86727669(3R)-1-[4-[5-[5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl]-1-methyl-1,2,4-triazol-3-yl]-1-piperidyl]-3-hydroxy-butan-1-one수율 51.2%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6342Acetonitrile용매

실험 절차

2-(1H-Benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (201 mg, 0.63 mmol) was added to a stirred suspension of 3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-(1-methyl-3-(piperidin-4-yl)-1H-1,2,4-triazol-5-yl)pyrazin-2-amine (200 mg, 0.52 mmol, described in Example 1), N-ethyl-N-isopropylpropan-2-amine (0.273 mL, 1.56 mmol) and (R)-3-hydroxybutanoic acid (65.2 mg, 0.63 mmol) in N,N-dimethylformamide (3 mL). The resulting suspension was stirred at room temperature for 2 hours. The resulting mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 30 mm diameter, 150 mm length, flow rate of 60 ml/minute) using an isocratic mixture of 31% acetonitrile in water (containing ammonium carbonate (2 g/L). The fractions containing the desired compound were evaporated to dryness to afford a pale yellow solid. This solid was stirred in acetonitrile (3 mL) at room temperature. The resulting solid was filtered, washed with cold acetonitrile and dried to afford the title compound (125 mg, 51.0%) as a pale yellow solid.

후처리

  1. customThe resulting mixture was purified by preparative HPLC
  2. additionan isocratic mixture of 31% acetonitrile in water (
  3. additioncontaining ammonium carbonate (2 g/L)
  4. additionThe fractions containing the desired compound
  5. customwere evaporated to dryness
  6. customto afford a pale yellow solid
  7. filtrationThe resulting solid was filtered
  8. washwashed with cold acetonitrile
  9. customdried

출처 및 근거

ORD 기록
ord-a7d188ee649e490d9e597932361d4dff
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156831B2

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