(2S)-2-Amino-N,3,3-trimethylbutanamide → N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)-3(S)-[1-(4-fluorophenyl)-1H-pyrrol-3-yl]succinamic acid benzyl ester

HRID 2299987Notes

Reaction equation

HRID 2299987 reaction equation
[CH2:1]([O:8][C:9](=[O:32])[CH2:10][C@@H:11](NC(OC(C)(C)C)=O)[C:12]([NH:14][C@H:15]([C:20](=[O:23])[NH:21][CH3:22])[C:16]([CH3:19])([CH3:18])[CH3:17])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC(=O)C[C@@H]([C:47]1[CH:51]=[CH:50][N:49]([C:52]2[CH:57]=[CH:56][C:55]([F:58])=[CH:54][CH:53]=2)[CH:48]=1)C(O)=O)C1C=CC=CC=1.CNC(=O)[C@H](C(C)(C)C)N.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CO.C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:32])[CH2:10][C@@H:11]([C:47]1[CH:51]=[CH:50][N:49]([C:52]2[CH:57]=[CH:56][C:55]([F:58])=[CH:54][CH:53]=2)[CH:48]=1)[C:12]([NH:14][C@H:15]([C:20](=[O:23])[NH:21][CH3:22])[C:16]([CH3:17])([CH3:18])[CH3:19])=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 445856(2S)-2-Amino-N,3,3-trimethylbutanamideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 537065323(R)-t-butoxycarbonylamino-N-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)succinamic acid benzyl esterHCID 54236521HCID 54236521, compound

Product 1

HCID 53772611N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)-3(S)-[1-(4-fluorophenyl)-1H-pyrrol-3-yl]succinamic acid benzyl esterYield 82%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

According to the procedure described in Example 1(b) for the preparation of 3(R)-t-butoxycarbonylamino-N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)succinamic acid benzyl ester, 2(S)-[1-(4-fluorophenyl)-1H-pyrrol-3-yl]-succinic acid 4-benzyl ester and L-t-leucine N-methylamide (see Malon, P.; Pancoska, P.; Budesinsky, M.; Hlavacek, J.; Pospisek, J.; Blaha, K. Coll. Czech. Chem Commun. 1983, 48, 2844-2861) were coupled with TBTU. Flash column chromatography with 0-5% MeOH/CH2Cl2 as gradient eluant provided in 82% yield N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)-3(S)-[1-(4-fluorophenyl)-1H-pyrrol-3-yl]succinamic acid benzyl ester as a crisp foam. 1H NMR: δ 7.34-7.26 (m, 7H), 7.10 (t, 2H, J=8.6 Hz), 6.95 (t, 1H, J=2.4 Hz), 6.89 (t, 1H, J=2.0 Hz), 6.49 (d, 1H, J=8.8 Hz), 6.23 (dd, 1H, J=1.8, 3.0 Hz), 5.76-5.74 (m, 1H), 5.11 (s, 2H), 4.12 (d, 1H, J=9.2 Hz), 4.00 (t, 1H, J=7.2 Hz), 3.20 (dd, 1H, J=7.7, 16.5 Hz), 2.84 (dd, 1H, J=6.6, 16.6 Hz), 2.75 (d, 3H, J=4.8 Hz), 0.95 (s, 9H). Anal. Calculated for C28H32N3O4F: C, 67.89; H, 8.48. Found: C, 67.78; H, 6.52; N, 8.50.

Sources & evidence

ORD record
ord-7b11ac8a1889480ba1daf54ad949e074
Source dataset
uspto-grants-2002_12
Patent number
US06495699B2

Reaction notes

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