Sodium Bicarbonate → HCID 58293011, compound

HRID 511379Notes

Reaction equation

HRID 511379 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][CH:32]=[C:33]2[C:37]=1[C:36](=[O:38])[N:35]([CH3:39])[CH:34]2[CH3:40].C([O-])(O)=O.[Na+]>>[CH3:40][CH:34]1[C:33]2[C:37](=[C:29]([NH:28][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:14]=[CH:15][C:16]([CH2:17][P:18](=[O:25])([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21])=[CH:26][CH:27]=4)[N:3]=3)[CH:30]=[CH:31][CH:32]=2)[C:36](=[O:38])[N:35]1[CH3:39]

Participants

4

Reactant 3

HCID 516892Sodium BicarbonateHCID 585226217-Amino-2,3-dimethyl-2,3-dihydro-isoindol-1-one2×HCID 86654003Diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate

Product 1

HCID 58293011HCID 58293011, compoundYield 66.5%

Procedure

The title compound was prepared according to the procedure from Example 102 using diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}benzyl)phosphonate (179.0 mg, 0.4224 mmol) and 7-amino-2,3-dimethyl-2,3-dihydro-1H-isoindol-1-one (Compound 157A, 83.7 mg, 0.475 mmol). The reaction mixture was poured into a separatory funnel containing saturated NaHCO3 and was extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude was purified using a Teledyne/ISCO Combiflash system, eluting first with 40-100% EtOAc:Heptane and then 0-15% MeOH:CH2Cl2. The product was purified again by MDP (under basic conditions; ammonium bicarbonate buffer (pH 9)) to afford the title product as an off-white solid (158.3 mg, 65%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.61 (br s, 1H), 9.93 (s, 1H), 8.71 (br s, 1H), 8.48 (s, 1H), 7.38-7.80 (m, 3H), 7.15-7.33 (m, 3H), 4.59 (q, J=6.6 Hz, 1H), 3.90-4.02 (m, 4H), 3.22 (d, J=21.5 Hz, 2H), 3.01 (s, 3H), 1.43 (d, J=6.6 Hz, 3H), 1.18 (t, J=6.9 Hz, 6H). MS (ES+): m/z 564.17 (100) [MH+]. HPLC: tR=1.56 min (TOF, polar—3 min).

Workup

  1. customThe title compound was prepared
  2. additionThe reaction mixture was poured into a separatory funnel
  3. extractionwas extracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude was purified
  9. washeluting first with 40-100% EtOAc
  10. customThe product was purified again by MDP (under basic conditions; ammonium bicarbonate buffer (pH 9))

Sources & evidence

ORD record
ord-6a5002217b6d40718491e694fdb25a4b
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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