Diisopropylethylamine → Gartisertib

HRID 524855

반응식

HRID 524855 반응식
[O:1]1[CH2:4][CH:3]([N:5]2[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[CH2:2]1.CCN(C(C)C)C(C)C.[NH2:20][C:21]1[C:30]([C:31]([NH:33][C:34]2[CH:35]=[N:36][CH:37]=[C:38]([F:49])[C:39]=2[N:40]2[CH2:45][CH2:44][CH:43]([C:46](O)=[O:47])[CH2:42][CH2:41]2)=[O:32])=[C:24]2[N:25]=[CH:26][C:27]([F:29])=[CH:28][N:23]2[N:22]=1.F[B-](F)(F)F.ClC1C=CC2N=NN(OC(=[N+](C)C)N(C)C)C=2C=1>C1COCC1.O>[NH2:20][C:21]1[C:30]([C:31]([NH:33][C:34]2[CH:35]=[N:36][CH:37]=[C:38]([F:49])[C:39]=2[N:40]2[CH2:45][CH2:44][CH:43]([C:46]([N:8]3[CH2:9][CH2:10][N:5]([CH:3]4[CH2:4][O:1][CH2:2]4)[CH2:6][CH2:7]3)=[O:47])[CH2:42][CH2:41]2)=[O:32])=[C:24]2[N:25]=[CH:26][C:27]([F:29])=[CH:28][N:23]2[N:22]=1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 24898642O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium TetrafluoroborateHCID 574162871-(Oxetan-3-yl)piperazineHCID 867209111-(3-(2-Amino-6-fluoropyrazolo[1,5-a]pyrimidine-3-carboxamido)-5-fluoropyridin-4-yl)piperidine-4-carboxylic acid

생성물 1

HCID 86720912Gartisertib수율 86.2%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 1-(oxetan-3-yl)piperazine (525 mg, 3.69 mmol) in THF (12 ml) was added DIPEA (1.72 ml, 9.91 mmol), followed by 1-(3-(2-amino-6-fluoropyrazolo[1,5-a]pyrimidine-3-carboxamido)-5-fluoropyridin-4-yl)piperidine-4-carboxylic acid (hydrochloride salt, 1.5 g, 3.3 mmol). [(6-chlorobenzotriazol-1-yl)oxy-(dimethylamino)methylene]-dimethyl-ammonium tetrafluoroborate (TCTU, 1.29 g, 3.64 mmol) was added and the mixture stirred under nitrogen until reaction completion (determined by HPLC analysis). The mixture was cooled and water (24 ml) was added dropwise. The mixture was allowed to warm to ambient and stirred for 3 hrs, then filtered. The filter cake was washed with (3×3 ml). The damp cake was dried under vacuum (with a nitrogen bleed) at 40° C. The product was obtained as a yellow solid (1.54 g, 86%); 1H NMR (500 MHz, DMSO-d6) δ 10.64 (s, 1H), 9.67 (s, 1H), 9.48 (dd, 1H), 9.26 (dd, 1H), 8.26 (d, 1H), 6.79 (s, 2H), 4.55 (t, 2H), 4.47 (t, 2H), 4.34 (t, 0.7H), 3.61 (dt, 4H), 3.48-3.41 (m, 2.5H), 3.22-3.17 (m, 2H), 3.05-3.03 (m, 2H), 3.99-2.93 (m, 1H), 2.28 (dt, 4H), 2.17-2.10 (m, 2H), 1.74 (d, 2H), 1.07 (t, 2H); 19F NMR (500 MHz, DMSO-d6) δ −152.8, −136.1; MS (ES+) 542.3.

후처리

  1. temperatureThe mixture was cooled
  2. temperatureto warm to ambient and
  3. stirringstirred for 3 hrs
  4. filtrationfiltered
  5. washThe filter cake was washed with (3×3 ml)
  6. customThe damp cake was dried under vacuum (with a nitrogen
  7. customat 40° C

출처 및 근거

ORD 기록
ord-c4fdfc820e7647c2963eac524f86e44a
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340546B2

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