Acetic Acid → 3-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(1-(1-isopropylpiperidin-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-isochromen-1-one formate

HRID 634408Notes

Reaction equation

HRID 634408 reaction equation
Cl.[NH2:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]2[N:9]([CH:13]([C:15]3[O:16][C:17](=[O:31])[C:18]4[C:23]([C:24]=3[C:25]3[CH2:26][CH2:27][NH:28][CH2:29][CH:30]=3)=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH3:14])[N:10]=[C:11]([I:12])[C:4]=12.[CH:32]([N:35]1[CH2:40][CH2:39][C:38](=O)[CH2:37][CH2:36]1)([CH3:34])[CH3:33].CCN(C(C)C)C(C)C.S([O-])([O-])(=O)=O.[Na+].[Na+].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.C(O)=O.O.CC#N>[CH:17]([OH:31])=[O:16].[NH2:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]2[N:9]([CH:13]([C:15]3[O:16][C:17](=[O:31])[C:18]4[C:23]([C:24]=3[C:25]3[CH2:26][CH2:27][N:28]([CH:38]5[CH2:39][CH2:40][N:35]([CH:32]([CH3:34])[CH3:33])[CH2:36][CH2:37]5)[CH2:29][CH:30]=3)=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH3:14])[N:10]=[C:11]([I:12])[C:4]=12

Participants

10

Reactant 6

HCID 176Acetic AcidHCID 24436Sodium SulfateHCID 793131-(Isopropyl)-4-piperidoneHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 1181311443-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(1,2,3,6-tetrahydropyridin-4-yl)-1H-isochromen-1-one hydrochloride

Product 1

HCID 1181312523-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(1-(1-isopropylpiperidin-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-isochromen-1-one formateYield 160.4%

Reagents, catalysts & solvents 3

HCID 284Formic AcidSolvent2×HCID 6344DichloromethaneSolventHCID 18373917Acetonitrile--water (1/1)Solvent2×

Procedure

A mixture of 3-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(1,2,3,6-tetrahydropyridin-4-yl)-1H-isochromen-1-one hydrochloride (Intermediate D23, 0.1 g, 0.182 mmol), 1-isopropylpiperidin-4-one (0.064 ml, 0.438 mmol), DIPEA (0.032 ml, 0.182 mmol) and a spatula of sodium sulfate in DCM (3 ml) was stirred at rt for 10 min. Acetic acid (0.061 mL, 1.09 mmol) was then added followed by sodium triacetoxyborohydride (154 mg, 0.726 mmol). The resulting suspension was stirred for 3 hrs at rt, then the reaction was quenched by the addition of 2 N HCl. The heterogeneous mixture was concentrated under reduced pressure. Purification by RP-flash chromatography (Biotage 30 g C18 column, gradient elution from 100:0 to 60:40 A/B in 15 CV; A: water/MeCN 95/5+0.01% HCOOH, B: water/MeCN 5/95+0.01% HCOOH) yielded title compound (99.8 mg, 0.146 mmol, 80% yield) as a light yellow powder.

Workup

  1. customthe reaction was quenched by the addition of 2 N HCl
  2. concentrationThe heterogeneous mixture was concentrated under reduced pressure
  3. customPurification by RP-flash chromatography (Biotage 30 g
  4. washC18 column, gradient elution from 100:0 to 60:40 A/B in 15 CV

Sources & evidence

ORD record
ord-8ff5eaa4837642ba9aaee50ad290e737
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

Loading…