Sodium Iodide → HCID 59394061, compound

HRID 450280Notes

Reaction equation

HRID 450280 reaction equation
Cl[CH2:2][C:3]1[CH:4]=[C:5]([NH:13][C:14]([N:16]2[C:24]3[C:19](=[CH:20][C:21]([O:25][C:26]4[C:27]5[CH2:35][CH2:34][N:33](C(OC(C)(C)C)=O)[CH2:32][C:28]=5[N:29]=[CH:30][N:31]=4)=[CH:22][CH:23]=3)[CH:18]=[CH:17]2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH:43]([NH2:46])([CH3:45])[CH3:44].[Na+].[I-]>>[CH:43]([NH:46][CH2:2][C:3]1[CH:4]=[C:5]([NH:13][C:14]([N:16]2[C:24]3[C:19](=[CH:20][C:21]([O:25][C:26]4[C:27]5[CH2:35][CH2:34][NH:33][CH2:32][C:28]=5[N:29]=[CH:30][N:31]=4)=[CH:22][CH:23]=3)[CH:18]=[CH:17]2)=[O:15])[CH:6]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:8]=1)([CH3:45])[CH3:44]

Participants

4

Reactant 3

HCID 5238Sodium IodideHCID 6363IsopropylamineHCID 67539289HCID 67539289, compound

Product 1

HCID 59394061HCID 59394061, compound

Conditions

Temperature
45 °C

Procedure

To a solution of the above mixture (0.15 g, 0.227 mmol) in 3 mL of DCM, isopropyl amine (0.06 mL, 0.680 mmol) is added followed by sodium iodide (0.1 g, 0.68 mmol). After 45 min, LC-MS shows that tert-butyl 4-(1-(3-((methylsulfonyloxy)methyl)-5-(trifluoromethyl)phenylcarbamoyl)-1H-indol-5-yloxy)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate is converted to desired product and the tert-butyl 4-(1-(3-(chloromethyl)-5-(trifluoromethyl)phenylcarbamoyl)-1H-indol-5-yloxy)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate left over. To the reaction 3 mL (0.227 mmol) of isopropyl amine is added followed by NaI (0.1 g, 0.68 mmol) and the mixture is heated to 45° C. for 2 h. The solvent is then removed and the residue diluted with EtOAc, washed with H2O, brine and the organic layer dried over Na2SO4. Following concentration the residue is separated by FCC (25-100% EtOAc/heptane). This product is then treated with 60 mL of 50% TFA/DCM at rt for 1.5 h. After concentration the residue is separated by semi-prep HPLC (C-18; 10-100% I/H2O with 0.1% NH4OH) to provide the title compound. MS (ESI) m/z 525.2 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 10.33 (s, 1H), 8.40 (s, 1H), 8.27 (d, J=8.8 Hz, 1H), 8.13 (d, J=3.8 Hz, 1H), 7.95 (d, J=15.2 Hz, 2H), 7.38-7.52 (m, 2H), 7.11 (dd, J=9.0, 2.4 Hz, 1H), 6.78 (d, J=3.8 Hz, 1H), 3.81 (d, J=7.6 Hz, 4H), 3.03 (t, J=5.8 Hz, 2H), 2.68-2.79 (m, 3H), 1.03 (d, J=6.1 Hz, 6H).

Workup

  1. additionis added
  2. customThe solvent is then removed
  3. additionthe residue diluted with EtOAc
  4. washwashed with H2O, brine
  5. dry with materialthe organic layer dried over Na2SO4
  6. concentrationconcentration the residue
  7. customis separated by FCC (25-100% EtOAc/heptane)
  8. additionThis product is then treated with 60 mL of 50% TFA/DCM at rt for 1.5 h
  9. concentrationAfter concentration the residue
  10. customis separated by semi-prep HPLC (C-18; 10-100% I/H2O with 0.1% NH4OH)

Sources & evidence

ORD record
ord-75a93969ffb748b6810ac2b3b540a28e
Source dataset
uspto-grants-2013_07
Patent number
US08486954B2

Reaction notes

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