Trifluoroacetic acid → N-[2,2-dimethyl-1(S)-(pyridin-4-ylcarbamoyl)propyl]-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid benzyl ester

HRID 613893Notes

Reaction equation

HRID 613893 reaction equation
C(OC(=O)C[C@@H](NC(OC(C)(C)C)=O)C([NH:14][C@H:15]([C:20](=[O:23])[NH:21]C)[C:16]([CH3:19])([CH3:18])[CH3:17])=O)C1C=CC=CC=1.FC(F)(F)C(O)=O.Cl.[CH2:41]([O:48][C:49](=[O:72])[CH2:50][C@@H:51]([N:55]1[CH:59]=[CH:58][C:57]([C:60]2[CH:65]=[CH:64][C:63]([C:66]3[CH:71]=[CH:70][N:69]=[CH:68][CH:67]=3)=[CH:62][CH:61]=2)=[CH:56]1)[C:52](O)=[O:53])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.CN(C(ON1N=[N:88][C:83]2[CH:84]=[CH:85][CH:86]=[CH:87]C1=2)=[N+](C)C)C.[B-](F)(F)(F)F>>[CH2:41]([O:48][C:49](=[O:72])[CH2:50][C@@H:51]([N:55]1[CH:59]=[CH:58][C:57]([C:60]2[CH:61]=[CH:62][C:63]([C:66]3[CH:71]=[CH:70][N:69]=[CH:68][CH:67]=3)=[CH:64][CH:65]=2)=[CH:56]1)[C:52]([NH:14][C@H:15]([C:20](=[O:23])[NH:21][C:85]1[CH:84]=[CH:83][N:88]=[CH:87][CH:86]=1)[C:16]([CH3:19])([CH3:18])[CH3:17])=[O:53])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Participants

5

Reactant 4

HCID 6422Trifluoroacetic acidHCID 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 700979932(R)-[3-(4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinic acid 4-benzyl ester hydrochloride

Product 1

HCID 54102944N-[2,2-dimethyl-1(S)-(pyridin-4-ylcarbamoyl)propyl]-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid benzyl esterYield 76%

Procedure

According to the procedure described in Example 1(b) for the preparation of N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)-3(R)-t-butoxycarbonylamino-succinamic acid benzyl ester, 2S-t-butoxycarbonylamino-3,3-dimethyl-N-(pyridin-4-yl)-butanamide (prepared as described in Example 5(d)) was deprotected with trifluoroacetic acid. The crude amine salt and 2(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinic acid 4-benzyl ester hydrochloride (prepared as described in Example 6(a)) were coupled with TBTU to provide after purification via column chromatography with 5% MeOH/CH2Cl2 and trituration with MTBE/hex, in 76% yield N-[2,2-dimethyl-1(S)-(pyridin-4-ylcarbamoyl)propyl]-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid benzyl ester as a pale yellow amorphous solid, which was used without further purification. 1H NMR: δ 8.65 (d, 2H, J=5.9 Hz), 8.43 (d, 2H, J=6.3 Hz), 8.26 (s, 1H), 7.64 (d, 2H, J=8.5 Hz), 7.58 (d, 2H, J=8.5 Hz), 7.53 (d, 2H, J=6.3 Hz), 7.40 (d, 2H, J=6.3 Hz), 7.32-7.24 (m, 5H), 7.12 (s, 1H), 6.85 (t 1H, J=2.4 Hz), 6.64 (dd, 1H, J=1.8, 2.9 Hz), 6.23 (d, 1H, J=8.1 Hz), 5.19-5.08 (m, 1H), 4.19 (d, 1H, J=8.1 Hz), 3.39 (dd, 1H, J=5.2, 16.9 Hz), 3.23 (dd, 1H, J=8.1, 17.3 Hz), 0.93 (s, 9H). Anal. Calculated for C37H37N5O4.0.9 H2O: C, 70.32; H, 6.19; N, 11.08. Found: C, 70.37; H, 6.11; N, 10.94.

Workup

  1. customto provide
  2. customafter purification via column chromatography with 5% MeOH/CH2Cl2 and trituration with MTBE/hex

Sources & evidence

ORD record
ord-e0f409546c424d6c8f12796586638f17
Source dataset
uspto-grants-1999_12
Patent number
US06008243

Reaction notes

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