Formic Acid → 3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(1-(azetidine-3-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-isochromen-1-one formate

HRID 634503Notes

Reaction equation

HRID 634503 reaction equation
Cl.[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:51])[C:25]4[C:30]([C:31]=3[C:32]3[CH2:33][CH2:34][N:35]([C:38]([CH:40]5[CH2:43][N:42](C(OC(C)(C)C)=O)[CH2:41]5)=[O:39])[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.O.CC#N.C(O)=O>O1CCOCC1>[CH:24]([OH:51])=[O:23].[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:51])[C:25]4[C:30]([C:31]=3[C:32]3[CH2:33][CH2:34][N:35]([C:38]([CH:40]5[CH2:41][NH:42][CH2:43]5)=[O:39])[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

6

Reactant 4

HCID 284Formic Acid2×HCID 313Hydrochloric AcidHCID 18373917Acetonitrile--water (1/1)2×HCID 118131360tert-butyl 3-(4-(3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-1-oxo-1H-isochromen-4-yl)-1,2,3,6-tetrahydropyridine-1-carbonyl)azetidine-1-carboxylate

Product 1

HCID 1181313363-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(1-(azetidine-3-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-isochromen-1-one formateYield 131.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

4 M HCl in 1,4-dioxane (2 ml, 8.00 mmol) was added to a stirred solution of tert-butyl 3-(4-(3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-1-oxo-1H-isochromen-4-yl)-1,2,3,6-tetrahydropyridine-1-carbonyl)azetidine-1-carboxylate (0.153 g, 0.224 mmol) in 1,4-dioxane (1 ml). After 1 h stirring at rt volatiles were removed under reduced pressure. Purification by RP flash chromatography (Biotage Isolera, 30 g C18 column, gradient elution from 100:0 to 80:20 A/B in 15 CV; A: water/MeCN 95/5+0.01% HCOOH, B: water/MeCN 5/95+0.01% HCOOH) yielded title compound (92.2 mg, 0.147 mmol, 65.5% yield) as a white powder.

Workup

  1. customwere removed under reduced pressure
  2. customPurification by RP flash chromatography (Biotage Isolera, 30 g
  3. washC18 column, gradient elution from 100:0 to 80:20 A/B in 15 CV

Sources & evidence

ORD record
ord-863d17b49b5e4218a1a4b38fb0585ea3
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

Loading…