4-Methylmorpholine → HCID 69587330, compound

HRID 720194Notes

Reaction equation

HRID 720194 reaction equation
[CH2:1]([CH:4]1[CH2:8][CH:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:6][N:5]1[C:17](=[O:28])[CH:18]([NH2:27])[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[CH:2]=[CH2:3].[C:29]([N:36]1[CH:45]([C:46](O)=[O:47])[CH2:44][CH:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH2:42]2)[CH2:37]1)([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30].ON1C2C=CC=CC=2N=N1.CN1CCOCC1.CN(C)CCCN=C=NCC>CN(C=O)C>[C:32]([O:31][C:29]([N:36]1[CH:45]([C:46](=[O:47])[NH:27][CH:18]([CH2:19][C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)[C:17]([N:5]2[CH2:6][CH:7]([O:9][CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:8][CH:4]2[CH2:1][CH:2]=[CH2:3])=[O:28])[CH2:44][C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH2:37]1)=[O:30])([CH3:35])([CH3:34])[CH3:33]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 21901733HCID 21901733, compoundHCID 69588055HCID 69588055, compound

Product 1

HCID 69587330HCID 69587330, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To solution of 1-(2-allyl-4-benzyloxy-pyrrolidin-1-yl)-2-amino-3-(4-fluorophenyl)-propan-1-one, 54, (1.4 mmol) is dissolved in DMF (10 mL) are added N-Boc-tetrahydroisoquinoline-3-carboxylic acid (0.47 g, 1.5 mmol), 1-hydroxybenzotriazole (0.43 g, 2.8 mmol), N-methylmorpholine (0.84 g, 8.3 mmol) and 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide (0.32 g, 1.7 mmol) at 0° C. The reaction mixture is stirred at 0° C. for 1 hour and then warmed to room temperature and stirred an additional 1.5 hour. The reaction is quenched with saturated NH4Cl solution and then extracted 3 times with EtOAc (70 mL). The organic layers are combined, washed with saturated NaCl solution, dried over Na2SO4, and the solvent is removed in vacuo. The crude product is purified over silica to afford 0.69 g (77% yield) of the desired product as a white solid. 1H NMR (300 MHz, MeOD, Rotamers) δ 6.90–7.41 (m, 13H), 5.55–5.81 (m, 1H), 4.32–5.12 (m, 8H), 3.94–4.18 (m, 2H), 2.75–3.89 (m, 6H), 2.39–2.64 (m, 1H), 1.78–2.29 (m, 2H), 1.20–1.64 (m, 10H); MS (ESMS) m/z 642.2 (M+H)+.

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred an additional 1.5 hour
  3. customThe reaction is quenched with saturated NH4Cl solution
  4. extractionextracted 3 times with EtOAc (70 mL)
  5. washwashed with saturated NaCl solution
  6. dry with materialdried over Na2SO4
  7. customthe solvent is removed in vacuo
  8. customThe crude product is purified over silica

Sources & evidence

ORD record
ord-10c8b611fc2f4b87893dc946f20b10ef
Source dataset
uspto-grants-2006_11
Patent number
US07132539B2

Reaction notes

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