4-Methylmorpholine → HCID 89499077, compound

HRID 336581Notes

Reaction equation

HRID 336581 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:15]2[CH2:24][C:23]([CH3:26])([CH3:25])[C:22]3[C:17](=[C:18]([C:27](O)=[O:28])[CH:19]=[CH:20][CH:21]=3)[CH2:16]2)=[N:6][C:7]=1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[S:30]1[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=2[N:32]=[C:31]1[NH2:39].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>>[S:30]1[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=2[N:32]=[C:31]1[NH:39][C:27]([C:18]1[CH:19]=[CH:20][CH:21]=[C:22]2[C:17]=1[CH2:16][N:15]([C:5]1[N:6]=[C:7]([C:8]([O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:9])[C:2]([Br:1])=[CH:3][CH:4]=1)[CH2:24][C:23]2([CH3:25])[CH3:26])=[O:28]

Participants

6

Reactant 5

HCID 79724-Methylmorpholine2×HCID 8706Benzo(d)thiazol-2-amine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 27960291-Hydroxybenzotriazole hydrate2×HCID 89498945HCID 89498945, compound

Product 1

HCID 89499077HCID 89499077, compound

Conditions

Temperature
40 °C

Procedure

An ambient solution of EXAMPLE 14B (182 mg), benzo[d]thiazol-2-amine (71.1 mg), 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride (113 mg), 1-hydroxybenzotriazole hydrate (91 mg), and N-methylmorpholine (0.065 mL) was stirred overnight. An additional 1 equivalent each of 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride, N-methylmorpholine, 1-hydroxybenzotriazole hydrate, and 2-aminobenzothiazole were added, and the reaction was heated to 40° C. for 4 hours. The reaction mixture was cooled to room temperature and quenched by the addition of saturated aqueous bicarbonate solution and ethyl acetate. The layers were separated, and the aqueous was extracted with additional 2× ethyl acetate. The combined organics were dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on silica gel with 0-50% ethyl acetate/hexanes to provide the title product.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customquenched by the addition of saturated aqueous bicarbonate solution and ethyl acetate
  3. customThe layers were separated
  4. extractionthe aqueous was extracted with additional 2× ethyl acetate
  5. dry with materialThe combined organics were dried with anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by chromatography on silica gel with 0-50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-6ab136acdb644663bb72f561600994cf
Source dataset
uspto-grants-2014_11
Patent number
US08889675B2

Reaction notes

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