4-Methylmorpholine → HCID 118345108, compound

HRID 593486Notes

Reaction equation

HRID 593486 reaction equation
[N:1]1([CH:10]([NH:14][C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[C:11](O)=[O:12])C2C=CC=CC=2N=N1.C(Cl)(=O)C(Cl)=O.[NH2:31][C:32]1[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:33]=1[C:40]([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=O.CN1CCOCC1>C1COCC1.C(Cl)Cl>[CH3:39][O:38][C:35]1[CH:36]=[CH:37][C:32]2[NH:31][C:11](=[O:12])[CH:10]([NH:14][C:15](=[O:16])[O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:1]=[C:40]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[C:33]=2[CH:34]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 65578Oxalyl chlorideHCID 4315963(1H-Benzotriazol-1-yl){[(benzyloxy)carbonyl]amino}acetic acidHCID 115866402-Benzoyl-4-methoxyaniline

Product 1

HCID 118345108HCID 118345108, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2-(1H-benzo[d][1,2,3]triazol-1-yl)-2-(benzyloxycarbonylamino)acetic acid (0.446 g, 1.965 mmol) in 5 mL of dry THF was cooled to 0° C. and then treated with oxalyl chloride (0.171 mL, 1.34 mmol). The mixture was stirred for 30 min at 0° C. A mixture of Intermediate 7A (0.235 g, 1.034 mmol) and NMM (0.237 mL, 2.59 mmol) in DCM (3 mL) was added to the above mixture. The resulting mixture was stirred at room temperature for 2 h and then filtered. The filtrate was treated with 2M methanolic ammonia (10 mL) and stirred at room temperature for 12 hrs. The mixture was then evaporated to dryness and the residue was treated with AcOH (5 mL) and stirred for 2 hrs at room temperature. The reaction mixture was then concentrated and purified by flash column chromatography to provide Intermediate 7B as a white solid: 70 mg (16.29%). HPLC: RT=1.908 min (ACN/H2O with TFA, UPLC R BEH C18, 1.7 μm, 2.1×50 mm, gradient=4 min, Flow=1.8 mL/min; Mobile Phase A: 0.1% TFA in water; Mobile Phase B: Acetonitrile; wavelength=220 nm); MS(ES): m/z=416 [M+H]+; 1H NMR (CDCl3) δ 8.681 (brs, 1H), 7.565-7.583 (d, J=7.2 Hz, 1H), 7.30-7.50 (m, 7H), 7.097 (brs, 2H), 6.80 (brs, 1H), 6.22 (d, J=8.4 Hz, 1H), 5.34 (d, J=7.2 Hz, 1H), 5.17 (s, 2H), 3.72 (s, 3H).

Workup

  1. additionwas added to the above mixture
  2. stirringThe resulting mixture was stirred at room temperature for 2 h
  3. filtrationfiltered
  4. additionThe filtrate was treated with 2M methanolic ammonia (10 mL)
  5. stirringstirred at room temperature for 12 hrs
  6. customThe mixture was then evaporated to dryness
  7. additionthe residue was treated with AcOH (5 mL)
  8. stirringstirred for 2 hrs at room temperature
  9. concentrationThe reaction mixture was then concentrated
  10. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-c98fac943ce24a94a107077b4da6350f
Source dataset
uspto-grants-2016_01
Patent number
US09242940B2

Reaction notes

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