Dimethylformamide → Z-Ala-Ala-Asn(Trt)-N(OCH3)CH3

HRID 1180363Notes

Reaction equation

HRID 1180363 reaction equation
[NH:1]([C:39]([O:41][CH2:42]C1C=CC=CC=1)=[O:40])[C@H:2]([C:4]([NH:6][C@H:7]([C:9]([NH:11][C@H:12]([C:36](O)=[O:37])[CH2:13][C:14](=[O:35])[NH:15][C:16](C1C=CC=CC=1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:10])[CH3:8])=[O:5])[CH3:3].Cl.[CH3:50][NH:51][O:52][CH3:53].C(N([CH2:59][CH3:60])CC)C.C(N=C=N[CH:67]([CH3:69])[CH3:68])(C)C.[CH:70]1[CH:71]=[CH:72][C:73]2N(O)N=N[C:74]=2[CH:75]=1.[CH3:80]N(C=O)C>C(Cl)Cl>[NH:1]([C:39]([O:41][CH2:42][C:60]1[CH:59]=[CH:68][CH:67]=[CH:69][CH:80]=1)=[O:40])[C@H:2]([C:4]([NH:6][C@H:7]([C:9]([NH:11][C@H:12]([C:36]([N:51]([CH3:50])[O:52][CH3:53])=[O:37])[CH2:13][C:14](=[O:35])[NH:15][C:16]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)([C:75]1[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:10])[CH3:8])=[O:5])[CH3:3]

Participants

8

Reactant 6

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 131726639Z-Ala-Ala-Asn(Trt)-OH

Product 1

HCID 131726640Z-Ala-Ala-Asn(Trt)-N(OCH3)CH3

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The Weinreb amide Z-Ala-Ala-Asn(Trt)-N(OCH3)CH3 (3) was prepared according to the method of Yasuma, 1998: To a stirred solution of Z-Ala-Ala-Asn(Trt)-OH (0.5 g, 0.77 mmol), N,O-dimethylhydroxylamine hydrochloride (79 mg, 0.81 mmol), and triethylamine (114 μl, 0.82 mmol) in dry DMF (3 ml) were added diisopropylcarbodiimide (131 μl, 0.85 mmol) and HOBt (115 mg, 0.85 mmol) at 0° C., and the whole was stirred for 16 h during which time it was allowed to warm to room temperature. The mixture was concentrated under reduced pressure. The obtained crude compound was dissolved in CH2Cl2 (25 ml) and washed with aqueous citric acid, water, aqueous NaHCO3, brine (5 ml per washing step). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to give the Weinreb amide as a white solid (0.49 g, 92%). The Weinreb amide was used without further purification.—TLC (MeOH/CHCl3, 1:30): Rf=0.49.—1H NMR (400 MHz, CDCl3): δ=1.26 (d, 3 H, J=7.0 Hz, CH3), 1.29 (d, 3 H, J=7.0 Hz, CH3), 2.64-2.76 (m, 2 H, CHCH2), 2.86 (s, 3 H, NCH3), 3.66 (s, 3 H, OCH3), 3.76-3.83 (m, 1 H, CH), 4.07-4.13 (m, 1 H, CH), 4.33-4.40 (m, 1 H, CH), 5.02-5.09 (m, 2 H, CH2O), 7.13-7.34 (m, 20 H, aryl-H).—MS (EI) m/z (%): 694 [M+H+], 716 [M+Na+], 732 [M+K+].

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customThe obtained crude compound
  3. washwashed with aqueous citric acid, water, aqueous NaHCO3, brine (5 ml per washing step)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-683fe9fc7f714df3a347a9916ae9b68b
Source dataset
uspto-grants-2007_10
Patent number
US07279550B2

Reaction notes

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