Acetic Acid → 3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-(dimethylamino)prop-1-yn-1-yl)-1H-isochromen-1-one hydrochloride

HRID 634510

Reaction equation

HRID 634510 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:20]([C:22]3[O:23][C:24](=[O:47])[C:25]4[C:30]([C:31]=3[C:32]#[C:33][CH2:34][N:35]([CH3:46])[C:36](=O)OCC3C=CC=CC=3)=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH3:21])[N:9]=[C:10]([C:11]3[CH:16]=[C:15]([O:17]C)[CH:14]=[C:13]([F:19])[CH:12]=3)[C:3]=12.O1CCCOO1.C(N(C)C(C)C)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.C(Cl)[Cl:81]>B(Br)(Br)Br.CCO>[ClH:81].[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:20]([C:22]3[O:23][C:24](=[O:47])[C:25]4[C:30]([C:31]=3[C:32]#[C:33][CH2:34][N:35]([CH3:46])[CH3:36])=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH3:21])[N:9]=[C:10]([C:11]3[CH:16]=[C:15]([OH:17])[CH:14]=[C:13]([F:19])[CH:12]=3)[C:3]=12

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 6344Dichloromethane3×HCID 547370N,N-DiisopropylmethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 19593658CID 19593658HCID 118150098Benzyl (3-(3-(1-(4-amino-3-(3-fluoro-5-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-1-oxo-1H-isochromen-4-yl)prop-2-yn-1-yl)(methyl)carbamate

Product 1

HCID 1181315153-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-(dimethylamino)prop-1-yn-1-yl)-1H-isochromen-1-one hydrochlorideYield 6.37%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 25134Boron tribromideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of benzyl (3-(3-(1-(4-amino-3-(3-fluoro-5-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-1-oxo-1H-isochromen-4-yl)prop-2-yn-1-yl)(methyl)carbamate (100 mg, 0.158 mmol) in DCM (4 ml), 1M BBr3 in DCM (3 ml, 10.50 mmol) was added and the reaction was stirred overnight. Then, the solution was cooled to 0° C. and stirred for 1 h. Then, EtOH (1 ml) was added and solvent was removed under reduced. The resulting material was reacted in DCM (4 ml) with trioxane (0.049 ml, 0.472 mmol), N-isopropyl-N-methylpropan-2-amine (18.14 mg, 0.157 mmol) for 30 min. Then, sodium triacetoxyborohydride (100 mg, 0.472 mmol) and acetic acid (28.4 mg, 0.472 mmol) were added and the reaction stirred for 1 h. Solvent was removed and crude was purified by C18 flash chromatography ((H2O/ACN)) 95:5+0.1% HCOOH}:{(ACN/H2O) 95:5+HCOOH 0.1%} from 100:0 to 0:100 affording the title compound (5 mg, 10.03 mmol, 6.37% yield) as a white solid.

Workup

  1. stirringstirred for 1 h
  2. customsolvent was removed
  3. stirringthe reaction stirred for 1 h
  4. customSolvent was removed
  5. customcrude was purified by C18 flash chromatography ((H2O/ACN)) 95:5+0.1% HCOOH

Sources & evidence

ORD record
ord-344db73ad0494d4195585ea9df0eed89
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Linked notes

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