Acetic Acid → HCID 57406016, 화합물

HRID 1520050

반응식

HRID 1520050 반응식
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O[C:20]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)=O)(C)(C)C.[CH3:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][N:33]=[C:32]2[C:38]1[N:39]=[N:40][N:41]([C:43]2[CH:50]=[CH:49][C:46](C=O)=[CH:45][CH:44]=2)[CH:42]=1.C(O)(=O)C.C([BH3-])#N.[Na+]>CC(N(C)C)=O>[CH3:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][N:33]=[C:32]2[C:38]1[N:39]=[N:40][N:41]([C:43]2[CH:44]=[CH:45][C:46]([CH2:20][N:22]3[CH2:23][CH2:24][NH:25][CH2:26][CH2:27]3)=[CH:49][CH:50]=2)[CH:42]=1

참가 물질

7

반응물 5

HCID 176Acetic AcidHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5003444Sodium cyanoborohydrideHCID 5049666Sodium triacetoxyborohydride2회HCID 715340964-[4-(5-methyl-1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]benzaldehyde

생성물 1

HCID 57406016HCID 57406016, 화합물

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

실험 절차

Sodium triacetoxyborohydride (279 mg; 1.32 mmol; 2.0 eq.) was added to a solution of tert-butyl-1-piperazinecarboxylate (1.22 g; 6.59 mmol; 10 eq.) and 4-[4-(5-methyl-1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]benzaldehyde (200 mg; 0.66 mmol; 1.0 eq.) in DMA (4 mL) and the reaction mixture was stirred overnight at RT. Sodium triacetoxyborohydride (279 mg; 1.32 mmol; 2.0 eq.) and glacial acetic acid (75.42 μl; 1.32 mmol; 2.00 eq.) then sodium cyanoborohydride (83 mg; 1.32 mmol; 2. eq.) were added to complete the reaction which was quenched with water and extracted with EtOAc (twice). Combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. The resulting gum was stirred at RT in a solution of HCl in dioxane (5 mL, 4N) for 2 hours. The reaction mixture was basified to pH=9-10 and extracted with EtOAc. Organic layer was dried over magnesium sulfate, filtered and concentrated. Purification by preparative HPLC afforded the title compound as a formic acid salt. It was dissolved in MeOH and passed through a SPE-NH2 cartridge. The fractions containing the desired compound were concentrated to dryness affording a yellow gum, which was twice sonicated in 3 mL of Et2O. The suspension obtained was concentrated then dried overnight under high vacuum to afford the title compound as a beige solid. 1H NMR (300 Mz, DMSO-d6) δ: 13.23 (brs, 1H), 9.25 (s, 1H), 8.14-8.13 (m, 1H), 8.00 (d, J=8.5 Hz, 2H), 7.54 (d, J=8.5 Hz, 2H), 7.50 (d, J=8.5 Hz, 1H), 7.28 (dd, J=8.5 Hz, 1.5 Hz, 1H), 3.52 (s, 2H), 2.72-2.69 (m, 4H), 2.487 (s, 3H), 2.32-2.30 (m, 4H). HPLC (Condition A): Rt 2.22 min (purity 95.4%). MS (ESI+): 374.3, MS (ESI−): 372.3.

후처리

  1. customthe reaction which
  2. customwas quenched with water
  3. extractionextracted with EtOAc (twice)
  4. washCombined organic phases were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. stirringThe resulting gum was stirred at RT in a solution of HCl in dioxane (5 mL, 4N) for 2 hours
  9. extractionextracted with EtOAc
  10. dry with materialOrganic layer was dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification by preparative HPLC

출처 및 근거

ORD 기록
ord-d42b143345654b8ca8a8c7a48df8541d
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073892B2

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