Water → 1-[5-tert-Butyl-2-(4-pyrrolidin-1-ylmethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt

HRID 1402460ノート

反応式

HRID 1402460 の反応式
[C:1]([C:5]1[CH:6]=[C:7]([NH:18][C:19]([NH:21][C@@H:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C@H:25]([O:32][C:33]3[CH:34]=[CH:35][C:36]4[N:37]([C:39]([N:42]5[CH2:47][CH2:46][CH2:45][CH2:44][C@@H:43]5[CH3:48])=[N:40][N:41]=4)[CH:38]=3)[CH2:24][CH2:23]2)=[O:20])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([CH:16]=O)=[CH:12][CH:11]=2)[N:9]=1)([CH3:4])([CH3:3])[CH3:2].[NH:49]1[CH2:53][CH2:52][CH2:51][CH2:50]1.[C:54]([O:57][BH-](OC(=O)C)OC(=O)C)(=[O:56])C.[Na+].O>C(Cl)Cl>[CH:54]([OH:57])=[O:56].[C:1]([C:5]1[CH:6]=[C:7]([NH:18][C:19]([NH:21][C@@H:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C@H:25]([O:32][C:33]3[CH:34]=[CH:35][C:36]4[N:37]([C:39]([N:42]5[CH2:47][CH2:46][CH2:45][CH2:44][C@@H:43]5[CH3:48])=[N:40][N:41]=4)[CH:38]=3)[CH2:24][CH2:23]2)=[O:20])[N:8]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:49]3[CH2:53][CH2:52][CH2:51][CH2:50]3)=[CH:12][CH:11]=2)[N:9]=1)([CH3:4])([CH3:2])[CH3:3]

参加物

6

反応物 4

HCID 962WaterHCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 866873141-[5-tert-Butyl-2-(4-formyl-phenyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea

生成物 1

HCID 866873181-[5-tert-Butyl-2-(4-pyrrolidin-1-ylmethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea formate salt

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of Intermediate 176b (0.188 mmol) and pyrrolidine (31.1 μL, 0.38 mmol) in DCM (3 mL), sodium triacetoxyborohydride (59.8 mg, 0.28 mmol) was added. The mixture was stirred at RT for 1 h. Water was added and the mixture extracted with DCM. The combined organics were passed through a phase separator and concentrated to dryness. The resulting residue was purified by RP-HPLC (C18, 18 mL/min, 20-85% MeCN in H2O+0.1% HCO2H) and the relevant fractions combined and concentrated to dryness. The title product was isolated as a light orange solid (49.5 mg). LCMS (Method 5): Rt 3.66 min, m/z 702.6 [MH+]. 1H NMR (400 MHz, d6-DMSO): 0.91 (3H, d, J=6.3 Hz), 1.27 (9H, s), 1.50 (2H, m), 1.69 (6H, m), 1.75-1.95 (4H, m), 1.98-2.17 (2H, m), 2.47 (4H, m, obscured by solvent), 2.90 (1H, m), 3.15 (1H, m, obscured by solvent), 3.63 (2H, s, obscured by solvent), 4.81 (1H, m), 5.51 (1H, t, J=4.3 Hz), 6.33 (1H, s), 7.09 (1H, d, J=8.9 Hz), 7.19 (1H, dd, J=9.6, 2.2 Hz), 7.24-7.38 (4H, m), 7.43 (4H, m), 7.64 (1H, d, J=9.6 Hz), 7.69 (1H, d, J=1.3 Hz), 8.09 (1H, s), 8.16 (1.4H, s).

後処理

  1. extractionthe mixture extracted with DCM
  2. concentrationconcentrated to dryness
  3. customThe resulting residue was purified by RP-HPLC (C18, 18 mL/min, 20-85% MeCN in H2O+0.1% HCO2H)
  4. concentrationconcentrated to dryness

出典と根拠

ORDレコード
ord-ec62e9c72e5f4583b05d26fb325a2c02
出典データセット
uspto-grants-2014_12
特許番号
US08907094B2

反応ノート

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