4-Amino-1-methylpiperidine → 4-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-fluoro-N-(1-methylpiperidin-4-yl)benzamide

Participants

Role	Name	HCID	Charge
Reactant	4-Amino-1-methylpiperidine	HCID 2737531	—
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	4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-fluoro-benzoic acid	HCID 58015083	—
Product	4-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-fluoro-N-(1-methylpiperidin-4-yl)benzamide	HCID 25253373	—

Reaction Steps

The title compound was synthesized from 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-fluorobenzoic acid as described in the General procedure for amide bond synthesis using HATU and 1-methylpiperidin-4-amine. The final compound was purified by reverse phase HPLC and basified to give the free base 1H NMR (400 MHz, DMSO-d6) δ ppm 1.50-1.75 (m, 12 H) 1.99 (m, 3 H) 2.19 (s, 3 H) 2.79 (m, 2 H) 3.74 (m, 1 H) 4.01 (t, J=14.0 Hz, 2 H) 4.68 (m, 1 H) 7.67 (d, J=8.6 Hz, 1 H) 7.72 (d, J=12.4 Hz, 1 H) 7.99 (t, J=8.2 Hz, 1 H) 8.20 (d, J=7.3 Hz, 1 H) 8.23 (s, 1 H) 9.08 (s, 1 H). [M+H] calc'd for C26H32F3N7O2, 532; found 532.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08318727B2
Source dataset	uspto-grants-2012_11
ORD ID	ord-de01ea094bf44b0cb179a61bd02391c4
Source note	uspto-grants-2012_11