Diisopropylethylamine → HCID 57463072, compound

HRID 1783820Notes

Reaction equation

HRID 1783820 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[N:14]([C:15]=2[C:16]2[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C@@H:23]4[CH2:28][CH2:27][CH2:26][NH:25][CH2:24]4)[N:17]=2)[CH:13]=[CH:12][O:11]3)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[Cl:38][C:39](Cl)([O:41]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[N:14]([C:15]=2[C:16]2[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C@@H:23]4[CH2:28][CH2:27][CH2:26][N:25]([C:39]([Cl:38])=[O:41])[CH2:24]4)[N:17]=2)[CH:13]=[CH:12][O:11]3)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 57463071HCID 57463071, compound

Product 1

HCID 57463072HCID 57463072, compoundYield 95.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]-N-[(3R)-piperidin-3-yl]pyrimidin-2-amine (200 mg, 0.45 mmol) and Hunig's base (145 μL, 0.90 mmol) in 10 mL DCM was added a solution of triphosgene (660 mg; 2.25 mmol) in 10 mL DCM dropwise over 10 min with stirring. The mixture was allowed to stir at ambient temperature for 1.5 hr. The reaction mixture was then concentrated under reduced pressure. The residue was diluted with 20 mL ether and concentrated under reduced pressure yielding (3R)-3-({4-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]pyrimidin-2-yl}amino)piperidine-1-carbonyl chloride as an off-white solid (190 mg). The solid was diluted in 10 mL DCM. To the resulting solution was added morpholine (60 μL, 0.67 mmol) and triethylamine (70 μL, 0.50 mmol). The mixture was allowed to stir at ambient temperature for 20 hr. The reaction mixture was then concentrated under reduced pressure and the residue purified by flash chromatography on silica gel (1:4, ethyl acetate:hexanes) to yield 4-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]-N-[(3R)-1-(morpholin-4-ylcarbonyl)piperidin-3-yl]pyrimidin-2-amine as an off-white solid (50.2 mg, 23%). 400 MHz 1H NMR (DMSO-d6) δ: 8.75 (s, 1H), 8.20 (s, 1H), 8.11 (d, J=5.2 Hz, 1H), 7.62-7.66 (m, 2H), 7.30-7.34 (m, 2H), 6.37 (s, 1H), 3.76 (m, 2H), 3.53 (m, 4H), 3.15 (m, 2H), 3.09 (m, 2H), 2.75 (m, 2H), 2.62 (m, 1H), 1.99 (s, 1H), 1.78 (br.s, 1H), 1.50-1.54 (m, 2H). LCMS: 492 [M+H].

Workup

  1. stirringto stir at ambient temperature for 1.5 hr
  2. concentrationThe reaction mixture was then concentrated under reduced pressure
  3. additionThe residue was diluted with 20 mL ether
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-14475ac02d574b14977a89ed6f061e41
Source dataset
uspto-grants-2009_03
Patent number
US07501430B2

Reaction notes

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