1-Hydroxybenzotriazole → t-Butyloxycarbonyl-L-glutaminyl-L-methionyl-L-alanyl-L-valyl-Nepsilon-benzyloxycarbonyl-L-lysine benzyl ester

HRID 1732524Notes

Reaction equation

HRID 1732524 reaction equation
[CH2:1]([O:8][C:9](=[O:54])[C@H:10]([CH2:39][CH2:40][CH2:41][CH2:42][NH:43][C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45])[NH:11][C:12](=[O:38])[C@H:13]([CH:35]([CH3:37])[CH3:36])[NH:14][C:15](=[O:34])[C@H:16]([CH3:33])[NH:17][C:18](=[O:32])[C@H:19]([CH2:28][CH2:29][S:30][CH3:31])[NH:20][C:21](OC(C)(C)C)=[O:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:55]([C:74]([O:76][C:77]([CH3:80])([CH3:79])[CH3:78])=[O:75])[C@H:56](C(OC1C=CC([N+]([O-])=O)=CC=1)=O)[CH2:57][CH2:58][C:59](=[O:61])[NH2:60].CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.C(OC(N[C@H](C(N[C@H](C(O)=O)CCSC)=O)CCC(=O)N)=O)(C)(C)C>>[CH2:1]([O:8][C:9](=[O:54])[C@H:10]([CH2:39][CH2:40][CH2:41][CH2:42][NH:43][C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45])[NH:11][C:12](=[O:38])[C@H:13]([CH:35]([CH3:36])[CH3:37])[NH:14][C:15](=[O:34])[C@H:16]([CH3:33])[NH:17][C:18](=[O:32])[C@H:19]([CH2:28][CH2:29][S:30][CH3:31])[NH:20][C:21](=[O:22])[C@H:56]([CH2:57][CH2:58][C:59](=[O:61])[NH2:60])[NH:55][C:74]([O:76][C:77]([CH3:80])([CH3:78])[CH3:79])=[O:75])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7017891L-Glutamine, N2-[(1,1-dimethylethoxy)carbonyl]-, 4-nitrophenyl esterHCID 12968638tert-Butyloxycarbonyl-L-glutaminyl-L-methionineHCID 86737377t-Butyloxycarbonyl-L-methionyl-L-alanyl-L-valyl-Nepsilon-benzyloxycarbonyl-L-lysine benzyl ester

Product 1

HCID 86737376t-Butyloxycarbonyl-L-glutaminyl-L-methionyl-L-alanyl-L-valyl-Nepsilon-benzyloxycarbonyl-L-lysine benzyl ester

Procedure

The Boc group was removed from a sample of compound XXII (2.5 g, 3.3 mmole) as described in previous paragraphs. The trifluoroacetate salt washed with ether and dried; the white solid (RfC, 0.76) showed on tlc a slight impurity at the origin (presumably the t-butylsulfonium salt). This material was acylated with Boc-L-Gln-ONp (1.4 g, 3.8 mmole, Bachem) in the presence of DIEA (1.3 ml, 8 mmole) and HOBt (0.58 ml, 3.8 mmole). Next day the product was isolated as described for XII and then purified by precipitation from a solution in DMF with H2O. The product was washed with H2O and dried: 28 g (93%), m.p. 238°-241° C. [α]D23 -27.7° (c 0.8, DMF); RfK, 0.43; RfL, 0.50.

Workup

  1. washThe trifluoroacetate salt washed with ether
  2. customdried
  3. customNext day the product was isolated
  4. custompurified by precipitation from a solution in DMF with H2O
  5. washThe product was washed with H2O
  6. customdried

Sources & evidence

ORD record
ord-0c235137c4a7476f97e5799982b8dd50
Source dataset
uspto-grants-1980_12
Patent number
US04237046

Reaction notes

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