4-Amino-1-Boc-piperidine → (R)-4-(9-cyclopentyl-7-fluoro-5-methyl-6-oxo-7-vinyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-(2-(dimethylamino)acetyl)piperidin-4-yl)-3-methoxybenzamide

HRID 1880956Notes

Reaction equation

HRID 1880956 reaction equation
[CH:1]1([N:7]2[CH2:13][C@:12]([F:16])([CH:14]=[CH2:15])[C:11](=[O:17])[N:10]([CH3:18])[C:9]3[CH:19]=[N:20][C:21]([NH:23][C:24]4[CH:32]=[CH:31][C:27]([C:28]([OH:30])=O)=[CH:26][C:25]=4[O:33][CH3:34])=[N:22][C:8]2=3)[CH2:6][CH2:5]C[CH2:3][CH2:2]1.[CH3:35][N:36]([C:38](ON1N=NC2C=CC=NC1=2)=[N+](C)C)[CH3:37].F[P-](F)(F)(F)(F)F.[C:59]([N:66]1[CH2:71][CH2:70][CH:69]([NH2:72])[CH2:68][CH2:67]1)([O:61]C(C)(C)C)=O>>[CH:1]1([N:7]2[CH2:13][C@:12]([F:16])([CH:14]=[CH2:15])[C:11](=[O:17])[N:10]([CH3:18])[C:9]3[CH:19]=[N:20][C:21]([NH:23][C:24]4[CH:32]=[CH:31][C:27]([C:28]([NH:72][CH:69]5[CH2:68][CH2:67][N:66]([C:59](=[O:61])[CH2:35][N:36]([CH3:38])[CH3:37])[CH2:71][CH2:70]5)=[O:30])=[CH:26][C:25]=4[O:33][CH3:34])=[N:22][C:8]2=3)[CH2:6][CH2:5][CH2:3][CH2:2]1

Participants

4

Reactant 3

HCID 12682914-Amino-1-Boc-piperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67117829(R)-4-(9-cyclohexyl-7-fluoro-7-vinyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid

Product 1

HCID 25253375(R)-4-(9-cyclopentyl-7-fluoro-5-methyl-6-oxo-7-vinyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-(1-(2-(dimethylamino)acetyl)piperidin-4-yl)-3-methoxybenzamide

Procedure

The title compound was synthesized from (R)-4-(9-cyclohexyl-7-fluoro-7-vinyl-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and 1-Boc-4-aminopiperidine. Further, after washing with water (10 ml), t-butoxycarbonyl (Boc) protection group was removed using 40% TFA in dichloromethane (6 ml). The resulting product was further acylated using N,N-dimethylacetyl chloride. The title product using preparative HPLC and neutralized with bicarbonate. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.41-2.05 (m, 12 H) 2.19 (s, 6 H) 2.92-3.21 (m, 4 H) 3.28 (s, 3 H) 3.72-3.87 (m, 2 H) 3.94 (s, 3 H) 3.99-4.20 (m, 2 H) 4.36 (d, J=15.41 Hz, 1 H) 4.89 (d, J=8.34 Hz, 1 H) 5.31-5.45 (m, 2 H) 6.01 (ddd, J=17.49, 12.69, 10.74 Hz, 1 H) 7.47 (d, J=1.77 Hz, 2 H) 7.83 (s, 1 H) 8.15 (d, J=7.83 Hz, 2 H) 8.31 (d, J=8.08 Hz, 1 H). [M+H] calc'd for C32H43FN8O4, 623; found 623.

Workup

  1. customas described in the General procedure for amide bond synthesis
  2. washFurther, after washing with water (10 ml), t-butoxycarbonyl (Boc) protection group
  3. customwas removed

Sources & evidence

ORD record
ord-cc7ac60334d44e2ba3f90ac60a58c0e0
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

Loading…