Diisopropylethylamine → HCID 59837484, compound

HRID 273051Notes

Reaction equation

HRID 273051 reaction equation
F[P-](F)(F)(F)(F)F.[N:8]1(OC(N(C)C)=[N+](C)C)[C:12]2C=CC=CC=2N=N1.Cl.[N:26]1([CH2:32][CH2:33][CH2:34][O:35][C:36]2[CH:41]=[CH:40][C:39]([C:42]3([C:48]([OH:50])=O)[CH2:47][CH2:46][O:45][CH2:44][CH2:43]3)=[CH:38][CH:37]=2)[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.Cl.CN.CCN(C(C)C)C(C)C>CN(C)C=O>[CH3:12][NH:8][C:48]([C:42]1([C:39]2[CH:40]=[CH:41][C:36]([O:35][CH2:34][CH2:33][CH2:32][N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[CH:37][CH:38]=2)[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1)=[O:50]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 6364545Methylamine hydrochlorideHCID 68577604HCID 68577604, compound

Product 1

HCID 59837484HCID 59837484, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

O-(1H-Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (640 mg, 1.7 mmol) was added to a solution of 4-[4-(3-Morpholin-4-yl-propoxy)-phenyl]-tetrahydro-pyran-4-carboxylic acid hydrochloride (500 mg, 1.3 mmol), methylamine hydrogen chloride (130 mg, 1.9 mmol) and Hunig's base (790 μL, 4.5 mmol) in N,N-dimethylformamide (5 mL). The mixture was stirred at room temperature for 2 hours and then concentrated in vacuo. The residue was partitioned between 2M NaOH solution (20 mL) and DCM (2×20 mL). The organics were combined, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 to 90:10:1, by volume) to provide the title compound (355 mg, 76%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 1.93-2.00 (m, 2H), 2.01-2.08 (m, 2H), 2.37-2.40 (m, 2H), 2.48 (m, 4H), 2.50 (t, 2H), 2.70 (d, 3H), 3.67-3.80 (m, 8H), 4.02 (t, 2H), 6.88 (d, 2H), 7.22 (d, 2H). LRMS APCI+ m/z 363 [MH]+.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was partitioned between 2M NaOH solution (20 mL) and DCM (2×20 mL)
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 to 90:10:1, by volume)

Sources & evidence

ORD record
ord-0a77269a7fe84ccb89d6879a18ae8305
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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