7-amino-4-(4-hydroxycyclohexyl)-2-methyl-2,3-dihydro-1H-isoindol-1-one → HCID 178479965, compound

HRID 511387Notes

Reaction equation

HRID 511387 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:33]=[CH:32][C:16]([CH2:17][P:18](=[O:31])([O:25][CH2:26][C:27]([F:30])([F:29])[F:28])[O:19][CH2:20][C:21]([F:24])([F:23])[F:22])=[CH:15][CH:14]=2)[N:3]=1.[NH2:34][C:35]1[CH:36]=[CH:37][C:38]([CH:46]2[CH2:51][CH2:50][CH:49]([OH:52])[CH2:48][CH2:47]2)=[C:39]2[C:43]=1[C:42](=[O:44])[N:41]([CH3:45])[CH2:40]2>>[OH:52][C@H:49]1[CH2:50][CH2:51][C@H:46]([C:38]2[CH:37]=[CH:36][C:35]([NH:34][C:2]3[C:7]([C:8]([F:10])([F:9])[F:11])=[CH:6][N:5]=[C:4]([NH:12][C:13]4[CH:33]=[CH:32][C:16]([CH2:17][P:18](=[O:31])([O:25][CH2:26][C:27]([F:29])([F:30])[F:28])[O:19][CH2:20][C:21]([F:23])([F:24])[F:22])=[CH:15][CH:14]=4)[N:3]=3)=[C:43]3[C:39]=2[CH2:40][N:41]([CH3:45])[C:42]3=[O:44])[CH2:47][CH2:48]1

Participants

3

Reactant 2

HCID 672549257-amino-4-(4-hydroxycyclohexyl)-2-methyl-2,3-dihydro-1H-isoindol-1-oneHCID 86654029Bis(2,2,2-trifluoroethyl) (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate2×

Product 1

HCID 178479965HCID 178479965, compound

Procedure

The title compound was prepared according to the procedure from Example 102 using bis(2,2,2-trifluoroethyl) (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate (Compound 165A, 35.7 mg, 0.0671 mmol) and 7-amino-4-(4-hydroxycyclohexyl)-2-methyl-2,3-dihydro-1H-isoindol-1-one (18.5 mg, 0.0711 mmol). The crude material was first purified on a Teledyne/ISCO system eluting with 50-100% EtOAc:Heptane followed by MDP (under acidic conditions; formic acid). The desired fractions were collected and concentrated in vacuo, giving the title material as an off-white solid, 24.3 mg (47%, 0.0315 mmol). 1H NMR (400 MHz, DMSOd6) δ ppm 10.59 (br s, 1H), 9.93 (s, 1H), 8.47 (s, 1H), 8.15-9.25 (m, 1H), 7.63 (d, J=6.1 Hz, 2H), 7.34 (d, J=8.6 Hz, 1H), 7.26 (dd, J=8.6, 2.5 Hz, 2H), 4.58-4.72 (m, 5H), 4.53 (s, 2H), 3.43-3.61 (m, 3H), 3.08 (s, 3H), 1.94 (dd, J=11.7, 2.1 Hz, 2H), 1.77 (d, J=11.6 Hz, 2H), 1.56 (dtd, J=12.9, 12.7, 2.1 Hz, 2H), 1.21-1.37 (m, 2H). MS (ES+): m/z 756.16 (100) [MH+]. HPLC: tR=4.14 min (ZQ3, polar—5 min).

Workup

  1. customThe crude material was first purified on a Teledyne/ISCO system
  2. washeluting with 50-100% EtOAc
  3. customThe desired fractions were collected
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fa4ace97d92f40aa953faab945bf5a1b
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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