Diisopropylethylamine → 1-(3-oxo-4H-1,4-benzoxazin-8-yl)-3-[[5-(trifluoromethyl)-2-pyridyl]methyl]urea

HRID 1505224

Reaction equation

HRID 1505224 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[C:19]2[O:20][CH2:21][C:22](=[O:24])[NH:23][C:18]=2[CH:17]=[CH:16][CH:15]=1.CCN(C(C)C)C(C)C.[F:34][C:35]([F:45])([F:44])[C:36]1[CH:37]=[CH:38][C:39]([CH2:42][NH2:43])=[N:40][CH:41]=1>C(Cl)Cl>[O:24]=[C:22]1[NH:23][C:18]2[CH:17]=[CH:16][CH:15]=[C:14]([NH:13][C:5]([NH:43][CH2:42][C:39]3[CH:38]=[CH:37][C:36]([C:35]([F:45])([F:34])[F:44])=[CH:41][N:40]=3)=[O:11])[C:19]=2[O:20][CH2:21]1

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 3796375[5-(Trifluoromethyl)pyridin-2-yl]methanamineHCID 115934888-Amino-2H-1,4-benzoxazin-3(4H)-one

Product 1

HCID 534767011-(3-oxo-4H-1,4-benzoxazin-8-yl)-3-[[5-(trifluoromethyl)-2-pyridyl]methyl]ureaYield 37%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of triphosgene (0.07 g, 0.37 mol eq) in anh. CH2Cl2 (10 mL) was slowly added the amine 1f (0.2 g, 1 mmol) solubilized in CH2Cl2 (10 mL) and DIEA (2.2 mol eq, 0.4 mL). After the addition was completed, the reaction mixture was stirred at room temp. for 15 min. Then the [5-(trifluoromethyl)-2-pyridyl]methanamine (1 mol eq, 0.18 g) solubilized in CH2Cl2 (10 mL) and DIEA (2.2 mol eq, 0.4 mL) was added in one portion. The mixture obtained was stirred at room temp. for 12 h. The solvent was removed at reduced pressure, water was added and the mixture was extracted with EtOAc (3×20 mL). The recombined organic phases were anhydrified over sodium sulfate and evaporated to dryness. The residue was purified by crystallization from EtOAc to obtain the product as yellow solid (0.132 g, 37% Yield). 1HNMR (DMSO, 400 MHz) δ 4.47 (d, 2H, J=6), 4.63 (s, 2H), 6.46 (dd, 1H, J=2), 6.80 (t, 1H, J=8), 7.57 m, 2H), 7.72 (dd, 1H, J=2), 8.18 (dd, 1H, J=2), 8.22 (s, 1H), 8.90 (m, 1H), 10.66 (s, 1H). [M+1] 366.94 (C16H13F3N4O3 requires 366.29).

Workup

  1. additionAfter the addition
  2. customThe mixture obtained
  3. stirringwas stirred at room temp. for 12 h
  4. customThe solvent was removed at reduced pressure, water
  5. additionwas added
  6. extractionthe mixture was extracted with EtOAc (3×20 mL)
  7. customevaporated to dryness
  8. customThe residue was purified by crystallization from EtOAc

Sources & evidence

ORD record
ord-adc487ee9b704eb580eb6be3e383c402
Source dataset
uspto-grants-2015_12
Patent number
US09216975B2

Linked notes

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