Diisopropylethylamine → Gartisertib

HRID 524855

反応式

HRID 524855 の反応式
[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

参加物

7

反応物 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

生成物 1

HCID 86720912Gartisertib収率 86.2%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-c4fdfc820e7647c2963eac524f86e44a
出典データセット
uspto-grants-2016_05
特許番号
US09340546B2

関連ノート

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