Water → 1-(5-tert-Butyl-2-{4-[(ethyl-methyl-amino)-methyl]-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 631008Notes

Reaction equation

HRID 631008 reaction equation
[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].[CH2:49]([NH:51][CH3:52])[CH3:50].[C:53]([O:56][BH-](OC(=O)C)OC(=O)C)(=[O:55])C.[Na+].O>C(Cl)Cl>[CH:53]([OH:56])=[O:55].[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:51]([CH2:49][CH3:50])[CH3:52])=[CH:12][CH:11]=2)[N:9]=1)([CH3:2])([CH3:4])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 12219N-MethylethylamineHCID 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

Product 1

HCID 866873201-(5-tert-Butyl-2-{4-[(ethyl-methyl-amino)-methyl]-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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of Intermediate 176b (0.188 mmol) and N-ethylmethylamine (32.3 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 (C, 18, 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 an off white solid (26.1 mg). LCMS (Method 5): Rt 3.65 min, m/z 690.6 [MH+]. 1H NMR (400 MHz, d6-DMSO): 0.91 (3H, d, J=6.4 Hz), 1.02 (3H, t, J=7.1 Hz), 1.27 (9H, s), 1.50 (2H, m), 1.66 (2H, m), 1.74-1.97 (4H, m), 1.98-2.11 (2H, m), 2.12 (3H, s), 2.40 (2H, q, J=7.1 Hz), 2.90 (1H, m), 3.16 (1H, m, obscured by solvent), 3.49 (2H, s, obscured by solvent), 4.81 (1H, m), 5.51 (1H, t, J=4.6 Hz), 6.33 (1H, s), 7.09 (1H, d, J=8.6 Hz), 7.19 (1H, dd, J=9.6, 2.1 Hz), 7.24-7.47 (8H, m), 7.64 (1H, d, J=10.2 Hz), 7.69 (1H, d, J=1.6 Hz), 8.09 (1H, s), 8.17 (1H, s).

Workup

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

Sources & evidence

ORD record
ord-0de0b876057749389185ce5cb119cf0d
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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