Isopropyl isocyanate → HCID 178457917, compound

HRID 2203282Notes

Reaction equation

HRID 2203282 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:22][N:12]3[C:13](=[O:21])[NH:14][C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=4[C:11]3=[N:10][CH2:9]2)=[CH:4][CH:3]=1.[CH:23]([N:26]=[C:27]=[O:28])([CH3:25])[CH3:24]>C1COCC1>[CH:23]([NH:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:22][N:12]3[C:13](=[O:21])[NH:14][C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=4[C:11]3=[N:10][CH2:9]2)=[CH:4][CH:3]=1)=[O:28])([CH3:25])[CH3:24]

Participants

4

Reactant 2

HCID 61277Isopropyl isocyanate2×HCID 178507413HCID 178507413, compound

Product 1

HCID 178457917HCID 178457917, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(4-aminophenyl)-2,3,4,7-tetrahydro-6H-pyrimido[1,2-c]quinazolin-6-one (20.2 mg, 0.069 mmol) in 1.6 mL THF was added isopropyl isocyanate (0.0074 mL, 0.076 mmol) and the reaction stirred at rt. After 45 min, the reaction was briefly warmed to approximately 50° C. and then allowed to cool to rt. After 2.5 hours, an additional 0.0074 mL (0.076 mmol) isopropyl isocyanate was added, the THF evaporated to 1 mL using a stream of nitrogen, the reaction briefly warmed to approximately 50° C. several times, and then stirred at rt overnight. At 21 hours, the reaction was quenched with MeOH, evaporated, then triturated with hot EtOAc to give the title compound as an off-white solid (15.6 mg, 60%). 1H NMR (DMSO-d6) δ: 10.67 (br. s, 1H), 8.25 (s, 1H), 7.97 (dd, J=8.1, 1.3 Hz, 1H), 7.40-7.46 (m, 1H), 7.34 (d, J=8.8 Hz, 2H), 7.16 (d, J=8.5 Hz, 2H), 6.98-7.09 (m, 2H), 5.96 (d, J=7.3 Hz, 1H), 4.15-4.24 (m, 1H), 3.65-3.80 (m, 2H), 3.44-3.59 (m, 2H), 2.86-2.98 (m, 1H), 1.10 (s, 3H), 1.08 (s, 3H).

Workup

  1. temperaturethe reaction was briefly warmed to approximately 50° C.
  2. temperatureto cool to rt
  3. waitAfter 2.5 hours
  4. customthe THF evaporated to 1 mL
  5. customthe reaction
  6. temperaturebriefly warmed to approximately 50° C. several times
  7. stirringstirred at rt overnight
  8. waitAt 21 hours
  9. customthe reaction was quenched with MeOH
  10. customevaporated
  11. customtriturated with hot EtOAc

Sources & evidence

ORD record
ord-2ac7da8b85fc47d09ea07a3454ece155
Source dataset
uspto-grants-2016_06
Patent number
US09365575B2

Reaction notes

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