Diisopropylethylamine → HCID 69182632, 화합물

HRID 132884

반응식

HRID 132884 반응식
FC(F)(F)C(O)=O.[CH3:8][CH:9]1[C:14]2[N:15]=[N:16][CH:17]=[CH:18][C:13]=2[CH2:12][CH2:11][NH:10]1.[C:19]([O:23][C:24]([NH:26][C@H:27]([CH2:32][C:33]1[CH:38]=[C:37]([F:39])[C:36]([F:40])=[CH:35][C:34]=1[F:41])[CH2:28][C:29](O)=[O:30])=[O:25])([CH3:22])([CH3:21])[CH3:20].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1C2N=CC=C(OC(N(C)C)=[N+](C)C)C=2N=N1.ON1C2N=CC=CC=2N=N1>CN(C=O)C>[C:19]([O:23][C:24]([NH:26][C@H:27]([CH2:32][C:33]1[CH:38]=[C:37]([F:39])[C:36]([F:40])=[CH:35][C:34]=1[F:41])[CH2:28][C:29]([N:10]1[CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][N:16]=[N:15][C:14]=2[CH:9]1[CH3:8])=[O:30])=[O:25])([CH3:22])([CH3:20])[CH3:21]

참가 물질

7

반응물 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 7146288(R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acid2회HCID 131726932HCID 131726932, 화합물2회HCID 178484478HCID 178484478, 화합물

생성물 1

HCID 69182632HCID 69182632, 화합물

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a solution of 73.9 mg (0.281 mmol) of 8-methyl-5,6,7,8-tetrahydropyrido[3,4-c]pyridazine, trifluoroacetate salt (Intermediate 34), 93.6 mg (0.281 mmol) of (3R)-3-[(tert-butoxycarbonyl)amino]4-(2,4,5-trifluorophenyl)butanoic acid (Intermediate 3) and 0.150 mL (0.843 mmol) of N,N-diisopropylethylamine in 2.5 ml of DMF were added O-(7-azabenzotriazol-yl)-N,N,N′,N′-tetra-methyluronium hexafluorophosphate (HATU; 128 mg, 0.337 mmol), 1-hydroxy-7-azabenzotriazole (HOAt; 45.9 mg, 0.337 mmol). The reaction was stirred at room temperature for 18 h. Then the reaction mixture was partitioned between ethyl acetate and 0.5M aqueous sodium bicarbonate solution. The aqueous phase was extracted with three portions of ethyl acetate. The combined organic phase was washed with brine, dried over magnesium sulfate and concentrated in vacuo. The mixture was purified by preparative TLC (100% ethyl acetate), then by chiral HPLC (ChiralCell OJ column, 14% ethanol/hexanes) to afford the title compound as a solid. The slower eluting isomer was used in Step B below. LC/MS: 409 (M+1-56).

후처리

  1. customThen the reaction mixture was partitioned between ethyl acetate and 0.5M aqueous sodium bicarbonate solution
  2. extractionThe aqueous phase was extracted with three portions of ethyl acetate
  3. washThe combined organic phase was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe mixture was purified by preparative TLC (100% ethyl acetate)

출처 및 근거

ORD 기록
ord-36489c892b754f54aa8facfc98630681
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07388019B2

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