Diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate → HCID 178476871, compound

HRID 1947958Notes

Reaction equation

HRID 1947958 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][CH:14]=2)[N:3]=1.[NH2:28][C:29]1[CH:30]=[CH:31][C:32]([C@H:40]2[CH2:45][CH2:44][C@@H:43]([O:46][CH2:47][CH3:48])[CH2:42][CH2:41]2)=[C:33]2[C:37]=1[C:36](=[O:38])[N:35]([CH3:39])[CH2:34]2>>[CH2:47]([O:46][C@@H:43]1[CH2:42][CH2:41][C@H:40]([C:32]2[CH:31]=[CH:30][C:29]([NH:28][C:2]3[C:7]([C:8]([F:9])([F:11])[F:10])=[CH:6][N:5]=[C:4]([NH:12][C:13]4[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][CH:14]=4)[N:3]=3)=[C:37]3[C:33]=2[CH2:34][N:35]([CH3:39])[C:36]3=[O:38])[CH2:45][CH2:44]1)[CH3:48]

Participants

3

Reactant 2

HCID 86654003Diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonateHCID 178468153HCID 178468153, compound2×

Product 1

HCID 178476871HCID 178476871, compoundYield 69%

Procedure

The title product was prepared according to the procedure for Example 102 using diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate (40.0 mg, 0.0944 mmol) and 7-amino-4-(cis-4-ethoxycyclohexyl)-2-methyl-2,3-dihydro-1H-isoindol-1-one (Compound 166A, 32.67 mg, 0.1133 mmol). The reaction mixture was concentrated under reduced pressure to yield a yellow oil. The material was purified by silica gel chromatography on the combi-flash Rf system using 1:1 EtOAc-DCM/MeOH (100:0→95:5) as eluent. The fractions containing product were combined and concentrated under reduced pressure to yield a white solid, 44.3 mg (69% yield). 1H NMR (DMSO-d6, 400 MHz): δ=1.13-1.22 (m, 9H), 1.46-1.59 (m, 4H), 1.70-1.84 (m, 2H), 1.91-2.01 (m, 2H), 2.56-2.68 (m, 1H), 3.08 (s, 3H), 3.16-3.24 (m, 2H), 3.45 (q, J=6.91 Hz, 2H), 3.61 (br. s., 1H), 3.91-4.01 (m, 4H), 4.53 (s, 2H), 7.25 (dd, J=8.59, 2.27 Hz, 2H), 7.30 (d, J=7.58 Hz, 1H), 7.60 (d, J=4.55 Hz, 2H), 8.46 (s, 1H), 8.51-8.88 (m, 1H), 9.87 (br. s., 1H), 10.58 (br. s., 1H). MS (ES+): m/z 676.30 [MH+] (TOF, polar).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto yield a yellow oil
  3. customThe material was purified by silica gel chromatography on the combi-flash Rf system
  4. additionThe fractions containing product
  5. concentrationconcentrated under reduced pressure
  6. customto yield a white solid, 44.3 mg (69% yield)

Sources & evidence

ORD record
ord-b7c00f04aeef4effbd8611470a5f420e
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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