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

HRID 634409Notes

Reaction equation

HRID 634409 reaction equation
CCN(C(C)C)C(C)C.Cl.[NH2:11][C:12]1[N:17]=[CH:16][N:15]=[C:14]2[N:18]([CH:22]([C:24]3[O:25][C:26](=[O:40])[C:27]4[C:32]([C:33]=3[C:34]3[CH2:35][CH2:36][NH:37][CH2:38][CH:39]=3)=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH3:23])[N:19]=[C:20]([I:21])[C:13]=12.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH3:66][N:67]([CH3:74])[CH2:68][CH2:69][CH2:70][C:71](O)=[O:72].C(=O)(O)[O-].[Na+]>C1COCC1.CN(C=O)C.C(O)=O.O.CC#N>[CH:26]([OH:40])=[O:25].[NH2:11][C:12]1[N:17]=[CH:16][N:15]=[C:14]2[N:18]([CH:22]([C:24]3[O:25][C:26](=[O:40])[C:27]4[C:32]([C:33]=3[C:34]3[CH2:35][CH2:36][N:37]([C:71](=[O:72])[CH2:70][CH2:69][CH2:68][N:67]([CH3:74])[CH3:66])[CH2:38][CH:39]=3)=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH3:23])[N:19]=[C:20]([I:21])[C:13]=12

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 126916404-(Dimethylamino)butyric acid hydrochlorideHCID 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 1181315133-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(1-(4-(dimethylamino)butanoyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-isochromen-1-one formateYield 125.1%

Reagents, catalysts & solvents 3

HCID 284Formic AcidSolvent2×HCID 18373917Acetonitrile--water (1/1)Solvent2×HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

DIPEA (0.253 ml, 1.452 mmol) was added at 0° C. to a stirred suspension 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, 0.200 g, 0.363 mmol), HATU (0.166 g, 0.436 mmol) and 4-dimethylaminobutyric acid hydrochloride (0.073 g, 0.436 mmol) in THF/DMF 5:1 (6 mL). The mixture was stirred at 0° C. for 15 min, then at rt for further 45 min. The reaction mixture was poured into saturated aqueous sodium bicarbonate and extracted with DCM. The collected organic phases were concentrated under reduced pressure and the crude purified by RP-flash chromatography (Biotage 30 g C18 column, gradient elution from 100:0 to 70:30 A/B in 15 CV; A: water/MeCN 95/5+0.01% HCOOH, B: water/MeCN 5/95+0.01% HCOOH) to give title compound (0.153 g, 0.227 mmol, 62.6% yield) as a white powder.

Workup

  1. waitat rt for further 45 min
  2. extractionextracted with DCM
  3. concentrationThe collected organic phases were concentrated under reduced pressure
  4. customthe crude purified by RP-flash chromatography (Biotage 30 g
  5. washC18 column, gradient elution from 100:0 to 70:30 A/B in 15 CV

Sources & evidence

ORD record
ord-a096d94372fa485dbfcb79236955c252
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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