Acetic Acid → HCID 118131401, compound

HRID 634465Notes

Reaction equation

HRID 634465 reaction equation
[ClH:1].[NH2:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]2[N:9]([CH:20]([C:22]3[O:23][C:24](=[O:38])[C:25]4[C:30]([C:31]=3[C:32]3[CH2:33][CH2:34][NH:35][CH2:36][CH:37]=3)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH3:21])[N:10]=[C:11]([C:12]3[CH:17]=[C:16]([OH:18])[CH:15]=[C:14]([F:19])[CH:13]=3)[C:4]=12.[CH:39](=O)[C:40]1[CH:45]=[CH:44][N:43]=[CH:42][CH:41]=1.CCN(C(C)C)C(C)C.[O-]S([O-])(=O)=O.[Na+].[Na+].CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[ClH:1].[NH2:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]2[N:9]([CH:20]([C:22]3[O:23][C:24](=[O:38])[C:25]4[C:30]([C:31]=3[C:32]3[CH2:33][CH2:34][N:35]([CH2:39][C:40]5[CH:45]=[CH:44][N:43]=[CH:42][CH:41]=5)[CH2:36][CH:37]=3)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH3:21])[N:10]=[C:11]([C:12]3[CH:17]=[C:16]([OH:18])[CH:15]=[C:14]([F:19])[CH:13]=3)[C:4]=12

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 133894-PyridinecarboxaldehydeHCID 24436Sodium SulfateHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 118131350HCID 118131350, compound

Product 1

HCID 118131401HCID 118131401, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(1,2,3,6-tetrahydropyridin-4-yl)-1H-isochromen-1-one hydrochloride (example 64, 37 mg, 0.064 mmol), isonicotinaldehyde (8.89 mg, 0.083 mmol) and DIEA (11.15 μl, 0.064 mmol) were dissolved in DCM (1.23 ml) followed by a spatula tip of anhydrous Na2SO4, and the mixture stirred rt for 10 min prior to add AcOH (10.97 μl, 0.192 mmol) and NaBH(OAc)3 (27.1 mg, 0.128 mmol). The resulting mixture was stirred for 1 h at rt, then quenched with 2M HClaqueous (1 ml), filtered to remove insoluble materials, and the filtrate purified via reverse phase chromatography using a Biotage C18 60 g SNAP with a gradient of water and acetonitrile to give (prior to drying a small amount of 1M HClaqueous was added) the title compound (10.6 mg, 26.5%) as white solid.

Workup

  1. stirringThe resulting mixture was stirred for 1 h at rt
  2. customquenched with 2M HClaqueous (1 ml)
  3. filtrationfiltered
  4. customto remove insoluble materials
  5. customthe filtrate purified via reverse phase chromatography
  6. customto give (prior
  7. customto drying a small amount of 1M HClaqueous
  8. additionwas added) the title compound (10.6 mg, 26.5%) as white solid

Sources & evidence

ORD record
ord-6acb2f84727545fb822e6123be971bbd
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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