7-amino-4-(3,4-dihydroxycyclopentyl)-2-methyl-2,3-dihydro-1H-isoindol-1-one trifluoroacetate → Diethyl(4-{[4-({7-[-3,4-dihydroxycyclopentyl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

HRID 1948057Notes

Reaction equation

HRID 1948057 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.FC(F)(F)C(O)=O.[NH2:37][C:38]1[CH:39]=[CH:40][C:41]([CH:49]2[CH2:53][CH:52]([OH:54])[CH:51]([OH:55])[CH2:50]2)=[C:42]2[C:46]=1[C:45](=[O:47])[N:44]([CH3:48])[CH2:43]2>CCOC(C)=O>[CH2:20]([O:19][P:18]([CH2:17][C:16]1[CH:26]=[CH:27][C:13]([NH:12][C:4]2[N:3]=[C:2]([NH:37][C:38]3[CH:39]=[CH:40][C:41]([CH:49]4[CH2:50][CH:51]([OH:55])[CH:52]([OH:54])[CH2:53]4)=[C:42]4[C:46]=3[C:45](=[O:47])[N:44]([CH3:48])[CH2:43]4)[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=2)=[C:14]([O:28][CH3:29])[CH:15]=1)(=[O:25])[O:22][CH2:23][CH3:24])[CH3:21]

Participants

4

Reactant 2

HCID 672550847-amino-4-(3,4-dihydroxycyclopentyl)-2-methyl-2,3-dihydro-1H-isoindol-1-one trifluoroacetate2×HCID 86654002Diethyl (4-{[4-chloro-5-(trifluoromethyl) pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

Product 1

HCID 76743909Diethyl(4-{[4-({7-[-3,4-dihydroxycyclopentyl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl}amino)-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

The title compound was prepared according to the procedure for Example 102 using diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (43 mg, 0.095 mmol) and 7-amino-4-(3,4-dihydroxycyclopentyl)-2-methyl-2,3-dihydro-1H-isoindol-1-one trifluoroacetate (salt) (Compound 243A, 36 mg, 0.096 mmol). The reaction mixture was diluted with EtOAc (30 mL), washed with sat. aq. NaHCO3 (2×10 mL), brine (10 mL), and dried over anhydrous sodium sulfate. The solvents were evaporated under reduced pressure, and the residue was purified by silica gel chromatography (ISCO Combi-flash system, eluting with 0-10% MeOH:DCM) to give the title compound as a white solid, 34 mg, 52% yield. 1H NMR (CDCl3): 1.26 (t, J=7.1 Hz, 6H), 1.95-2.01 (m, 2H), 2.23-2.29 (m, 2H), 3.17 (d, J=21.7 Hz, 2H), 3.21 (s, 3H), 3.53 (m, 1H), 3.91 (s, 3H), 3.97-4.07 (m, 4H), 4.35 (s, 2H), 4.39-4.43 (m, 2H), 6.84 (s, 1H), 6.94 (m, 1H), 7.32 (d, J=8.8 Hz, 1H), 7.67 (s, 1H), 8.26 (d, J=8.1 Hz, 1H), 8.38 (s, 1H), 8.54 (d, J=8.6 Hz, 1H), 10.31 (s, 1H). MS (ES+): m/z=680.14 [MH+]. HPLC: tR=3.60 min (ZQ3, polar—5 min).

Workup

  1. customThe title compound was prepared
  2. washwashed with sat. aq. NaHCO3 (2×10 mL), brine (10 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvents were evaporated under reduced pressure
  5. customthe residue was purified by silica gel chromatography (ISCO Combi-flash system, eluting with 0-10% MeOH:DCM)

Sources & evidence

ORD record
ord-95604d166e164947a0e6ce98b877f00b
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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