Methylamine → N-methyl-3(R)-[3-[4-(pyndin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid benzyl ester

HRID 2299971Notes

Reaction equation

HRID 2299971 reaction equation
[CH2:1]([O:8][C:9](=[O:32])[CH2:10][C@@H:11]([NH:24][C:25](OC(C)(C)C)=O)[C:12]([NH:14][C@H:15](C(=O)NC)C(C)(C)C)=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=C1[C@@H](NC(=O)[C@H:53]([N:58]2[CH:62]=[CH:61][C:60]([C:63]3[CH:68]=[CH:67][C:66]([C:69]4[CH:74]=CC=CN=4)=[CH:65][CH:64]=3)=[CH:59]2)CC(O)=O)CC2=CN(C3C2=CC=CC=3)CCOCCN1.CN.[CH3:79]N(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>>[CH2:1]([O:8][C:9](=[O:32])[CH2:10][C@@H:11]([N:24]1[CH:25]=[CH:74][C:69]([C:66]2[CH:65]=[CH:64][C:63]([C:60]3[CH:59]=[CH:53][N:58]=[CH:62][CH:61]=3)=[CH:68][CH:67]=2)=[CH:79]1)[C:12]([NH:14][CH3:15])=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 6329MethylamineHCID 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 70157731N-(8-oxo-4-oxa-1,7-diazatricyclo[9.6.1.012,17]octadeca-11(18),12,14,16-tetraen-9(S)-yl)-3(R)-[3-[4-(pyridinyl)phenyl]-1H-pyrrol-1-yl]succinamic acid

Product 1

HCID 53874083N-methyl-3(R)-[3-[4-(pyndin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid benzyl esterYield 51%

Procedure

According to the procedure described in Example 1(b) for the preparation of 3(R)-t-butyloxycarbonylamino-N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)succinamic acid benzyl ester, 2(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinic 4-benzyl ester hydrochloride (prepared as described in Example 7(a)) and excess 40% aqueousueous methylamine were coupled with TBTU. The solid that precipitated from the reaction mixture was washed with water and, after drying, with ethyl acetate to give 51% of N-methyl-3(R)-[3-[4-(pyridin-4-yl)phenyl]-1H-pyrrol-1-yl]succinamic acid benzyl ester as a yellow solid: 1HNMR (DMSO-d6): δ—8.58 (d, 2H, J=4.4 Hz), 7.84 (br s, 1H), 7.76-7.70 (m, 4H), 7.60 (d, 2H, J=8.5 Hz), 7.29-7.25 (m, 6H), 6.76 (s, 1H), 6.40 (s, 1H), 5.03 (s, 2H), 4.67 (t, 1H, J=6.2 Hz), 3.20 (dd, 1H, J=15.8, 6.2 Hz), 2.86 (dd, 1H, J=16.0, 8.6 Hz), 2.32 (s, 3H); Anal. Calculated for C27H25N3O3.1.3H2O: C, 70.05; H, 6.01; N, 9.08. Found: C, 69.98, 69.97; H, 5.98, 6.00; N, 9.01, 9.00.

Workup

  1. customThe solid that precipitated from the reaction mixture
  2. washwas washed with water
  3. dry with materialafter drying, with ethyl acetate

Sources & evidence

ORD record
ord-35c0528dbecb4c7395c29c7fd02e54db
Source dataset
uspto-grants-2002_12
Patent number
US06495699B2

Reaction notes

Loading…