Acetic Acid → HCID 118131363, compound

HRID 634523Notes

Reaction equation

HRID 634523 reaction equation
[CH:1]([OH:3])=[O:2].[NH2:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]2[N:11]([CH:22]([C:24]3OC(=O)[C:27]4[C:32]([C:33]=3[C:34]3[CH2:35][NH:36][CH2:37][CH2:38][CH:39]=3)=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH3:23])[N:12]=[C:13]([C:14]3[CH:19]=[C:18]([OH:20])[CH:17]=[C:16]([F:21])[CH:15]=3)[C:6]=12.[CH3:41][N:42]1[CH2:47][CH2:46][C:45](=O)[CH2:44][CH2:43]1.CCN(C(C)C)C(C)C.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(Cl)[Cl:77]>>[ClH:77].[ClH:77].[NH2:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]2[N:11]([CH:22]([C:24]3[O:2][C:1](=[O:3])[C:27]4[C:32]([C:33]=3[C:34]3[CH2:35][N:36]([CH:45]5[CH2:46][CH2:47][N:42]([CH3:41])[CH2:43][CH2:44]5)[CH2:37][CH2:38][CH:39]=3)=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH3:23])[N:12]=[C:13]([C:14]3[CH:19]=[C:18]([OH:20])[CH:17]=[C:16]([F:21])[CH:15]=3)[C:6]=12

Participants

7

Reactant 6

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 740491-Methyl-4-piperidoneHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 118131274HCID 118131274, compound

Product 1

HCID 118131363HCID 118131363, compoundYield 68%

Procedure

To a solution of 3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(1,2,5,6-tetrahydropyridin-3-yl)-1H-isochromen-1-one formate (example 171, 0.03 g, 0.055 mmol), 1-methylpiperidin-4-one (0.08 ml, 0.066 mmol) and DIPEA (0.009 ml, 0.055 mmol) in DCM (2 ml) dry Na2SO4 was added and the mixture stirred at RT for 10 min. AcOH (0.009 ml, 0.165 mmol) and sodium triacetoxyborohydride (0.023 g, 0.11 mmol) were added in this order and the reaction mixture was stirred for 3 hrs at RT. The reaction was quenched by the addition of 2M HCl (2 ml), the mixture was filtered and the filtrate was purified by reverse phase flash chromatography on Biotage C18 cartridge (water/MeCN 90/10+0.1% HCOOH to water/MeCN 5/95+0.01% HCOOH). Before drying 2M HCl (2 ml) was added and the mixture was dried under reduced pressure to afford title compound (0.025 g, 0.037 mmol, 68%).

Workup

  1. stirringthe reaction mixture was stirred for 3 hrs at RT
  2. customThe reaction was quenched by the addition of 2M HCl (2 ml)
  3. filtrationthe mixture was filtered
  4. customthe filtrate was purified by reverse phase flash chromatography on Biotage C18 cartridge (water/MeCN 90/10+0.1% HCOOH to water/MeCN 5/95+0.01% HCOOH)
  5. dry with materialBefore drying 2M HCl (2 ml)
  6. additionwas added
  7. customthe mixture was dried under reduced pressure

Sources & evidence

ORD record
ord-2fa2aee70fe84028985252240323918c
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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