Water → HCID 178479963, compound

HRID 511498Notes

Reaction equation

HRID 511498 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([Cl:9])=[CH:4][N:3]=1.[NH2:10][C:11]1[CH:12]=[CH:13][C:14]([C@H:22]2[CH2:27][CH2:26][C@H:25]([OH:28])[CH2:24][CH2:23]2)=[C:15]2[C:19]=1[C:18](=[O:20])[N:17]([CH3:21])[CH2:16]2.CCN(C(C)C)C(C)C.O>CC(N(C)C)=O.CCOC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([C@H:22]3[CH2:27][CH2:26][C@H:25]([OH:28])[CH2:24][CH2:23]3)=[C:15]3[C:19]=2[C:18](=[O:20])[N:17]([CH3:21])[CH2:16]3)[C:5]([Cl:9])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 2372592,4,5-TrichloropyrimidineHCID 178479967HCID 178479967, compound

Product 1

HCID 178479963HCID 178479963, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2,4,5-trichloropyrimidine (550.5 mg, 3.001 mmol) and 7-amino-4-(trans-4-hydroxycyclohexyl)-2-methyl-2,3-dihydro-1H-isoindol-1-one (166.6 mg, 0.6400 mmol) in DMA (8 mL) was charged with DIPEA (1 mL, 6 mmol) and then heated to 100° C. overnight. The reaction mixture was cooled to ambient temperature, diluted with EtOAc, and poured into water. The material was extracted thrice with EtOAc and the combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude material was adsorbed onto a pre-filled solid loading cartridge [RediSepRf 25 gram] and purified using the Teledyne/ISCO system [RediSepRf 12 gram silica], eluting first with 0-100% EtOAc:CH2Cl2 and then 0-5% MeOH:CH2Cl2. The desired fractions were pooled together and concentrated in vacuo, giving the title material as a brown solid, 173.0 mg. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.07 (s, 1H), 8.52 (s, 1H), 8.43 (d, J=8.6 Hz, 1H), 7.52 (d, J=8.6 Hz, 1H), 4.60 (d, J=4.5 Hz, 1H), 4.57 (s, 2H), 3.48 (ddd, J=15.0, 6.4, 4.4 Hz, 1H), 3.10 (s, 3H), 1.93 (br s, 2H), 1.77 (br d, J=12.4 Hz, 2H), 1.55 (dtd, J=13.0, 12.7, 2.5 Hz, 2H), 1.22-1.37 (m, 3H). MS (ES+): m/z 407.10/409.10 (100/72) [MH+]. HPLC: tR=1.40 min (TOF, polar—3 min).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. extractionThe material was extracted thrice with EtOAc
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified
  8. washeluting first with 0-100% EtOAc
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-57caa22b88ae4866b042984b7106cf95
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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