Diisopropylethylamine → (R)-2-(3-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)piperidine-1-carbonyl)-3-cyclopropylacrylonitrile

Participants

Role	Name	HCID	Charge
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
Reactant	2-Cyano-3-cyclopropylprop-2-enoic acid	HCID 70513033	—
Reactant	(R)-5-(4-phenoxyphenyl)-7-(piperidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine	HCID 71014248	—
Solvent	Dichloromethane	HCID 6344	—
Product	(R)-2-(3-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)piperidine-1-carbonyl)-3-cyclopropylacrylonitrile	HCID 86714514	54%

Reaction Steps

To a mixture of (R)-5-(4-phenoxyphenyl)-7-(piperidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (100 mg, 0.26 mmol, 1.0 eq), 2-cyano-3-cyclopropylacrylic acid (45 mg, 0.32 mmol, 1.2 eq) and DIPEA (102 mg, 0.78 mmol, 3 eq) in 10 mL DCM was added HATU (150 mg, 0.40 mmol, 1.5 eq) and the reaction mixture was stirred for 4 h at RT under N2. The reaction mixture was purified by Pre-TLC to give the title compound (60 mg, 54% in yield). LCMS: m/z (505.0) (M+H)+ 1HNMR (400 MHz, CDCl3): δ 0.826˜0.837 (m, 2H), 1.147˜1.183 (m, 6H), 1.744˜2.210 (m, 5H), 4.661˜4.699 (m, 1H), 5.212˜5.226 (m, 2H), 6.499˜6.524 (m, 1H), 6.921˜7.367 (m, 10H) and 8.223 (S, 1H).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08759358B1
Source dataset	uspto-grants-2014_06
ORD ID	ord-4f2777e4670d48818ae248b21dd9f108
Source note	uspto-grants-2014_06