4-[4-(4-acetylpiperazin-1-yl)cyclohexyl]-7-amino-2-methyl-2,3-dihydro-1H-isoindol-1-one → HCID 178476861, compound

HRID 511486Notes

Reaction equation

HRID 511486 reaction equation
Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:27]=[CH:26][C:16]([CH2:17][P:18](=[O:25])([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21])=[CH:15][C:14]=2[O:28][CH3:29])[N:3]=1.[C:30]([N:33]1[CH2:38][CH2:37][N:36]([CH:39]2[CH2:44][CH2:43][CH:42]([C:45]3[CH:53]=[CH:52][C:51]([NH2:54])=[C:50]4[C:46]=3[CH2:47][N:48]([CH3:56])[C:49]4=[O:55])[CH2:41][CH2:40]2)[CH2:35][CH2:34]1)(=[O:32])[CH3:31]>>[C:30]([N:33]1[CH2:38][CH2:37][N:36]([C@H:39]2[CH2:40][CH2:41][C@H:42]([C:45]3[CH:53]=[CH:52][C:51]([NH:54][C:2]4[C:7]([C:8]([F:9])([F:11])[F:10])=[CH:6][N:5]=[C:4]([NH:12][C:13]5[CH:27]=[CH:26][C:16]([CH2:17][P:18](=[O:25])([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21])=[CH:15][C:14]=5[O:28][CH3:29])[N:3]=4)=[C:50]4[C:46]=3[CH2:47][N:48]([CH3:56])[C:49]4=[O:55])[CH2:43][CH2:44]2)[CH2:35][CH2:34]1)(=[O:32])[CH3:31]

Participants

3

Reactant 2

HCID 672564554-[4-(4-acetylpiperazin-1-yl)cyclohexyl]-7-amino-2-methyl-2,3-dihydro-1H-isoindol-1-one2×HCID 86654002Diethyl (4-{[4-chloro-5-(trifluoromethyl) pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

Product 1

HCID 178476861HCID 178476861, compound

Procedure

The title compounds were prepared according to the procedure for Example 102 using diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate and 4-[4-(4-acetyl piperazin-1-yl)cyclohexyl]-7-amino-2-methyl-2,3-dihydro-1H-isoindol-1-one (Compound 237A). The reaction mixture was purified by MDP. Example 237 was first peak to elute. 1H NMR (CDCl3, 400 MHz): δ=1.28 (t, J=6.95 Hz, 6 H), 1.50-1.73 (m, 7 H), 2.02 (s, 2 H), 2.12 (s, 3 H), 2.50 (br. s., 2 H), 2.62 (br. s., 3 H), 3.13-3.21 (m, 2 H), 3.22 (s, 3 H), 3.42-3.75 (m, 4 H), 3.93 (s, 3 H), 3.99-4.10 (m, 4 H), 4.38 (s, 2 H), 6.90 (dt, J=8.08, 2.15 Hz, 1H), 6.94 (t, J=2.02 Hz, 1 H), 7.34 (d, J=8.84 Hz, 1 H), 7.63 (s, 1 H), 8.28 (d, J=7.58 Hz, 1H), 8.40 (s, 1 H), 8.64 (d, J=8.59 Hz, 1 H), 10.51 (s, 1 H). MS (ES+): m/z 788.31 [MH+] (TOF, polar). Example 238 eluted afterwards: 1H NMR (CDCl3, 400 MHz): δ=1.28 (t, J=7.07 Hz, 6 H), 1.87 (d, J=4.04 Hz, 2 H), 1.91-2.03 (m, 2 H), 2.12-2.25 (m, 7 H), 2.84 (br. s., 2 H), 3.21 (s, 3 H), 3.23-3.33 (m, 4 H), 3.86 (s, 3 H), 3.93 (br. s., 2 H), 4.04 (qdd, J=7.31, 7.31, 7.31, 7.14, 1.77 Hz, 4 H), 4.38 (s, 2 H), 6.94-7.00 (m, 2 H), 7.36 (d, J=7.83 Hz, 1 H), 7.71 (br. s., 1 H), 8.23 (br. s., 2 H), 11.20 (br. s., 1 H). MS (ES+): m/z 788.31 [MH+] (TOF, polar).

Workup

  1. customThe reaction mixture was purified by MDP
  2. washto elute
  3. washExample 238 eluted afterwards

Sources & evidence

ORD record
ord-fd83c2a52a4a487d877fbc35256e79b6
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

Loading…