Acetic Acid → 3(R)-[3-[(4-cyanophenyl)acetyl]-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acid allyl ester

HRID 566763Notes

Reaction equation

HRID 566763 reaction equation
FC(F)(F)C(O)=[O:4].[CH2:8]([O:11][C:12](=[O:28])[CH2:13][C@@H:14]([NH2:27])[C:15]([NH:17][C@H:18]([C:23](=[O:26])[NH:24][CH3:25])[C:19]([CH3:22])([CH3:21])[CH3:20])=[O:16])[CH:9]=[CH2:10].[C:29]([C:31]1[CH:36]=[CH:35][C:34]([C:37]#[C:38][CH:39]2[CH2:43][CH:42](OC)O[CH:40]2OC)=[CH:33][CH:32]=1)#[N:30].FC(F)(F)C(O)=O.CC(O)=O>CCCCCCC>[CH2:8]([O:11][C:12](=[O:28])[CH2:13][C@@H:14]([N:27]1[CH:42]=[CH:43][C:39]([C:38](=[O:4])[CH2:37][C:34]2[CH:35]=[CH:36][C:31]([C:29]#[N:30])=[CH:32][CH:33]=2)=[CH:40]1)[C:15]([NH:17][C@H:18]([C:23](=[O:26])[NH:24][CH3:25])[C:19]([CH3:20])([CH3:21])[CH3:22])=[O:16])[CH:9]=[CH2:10]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 183803483-[2-(4-Cyanophenyl)-ethynyl]-2,5-dimethoxy-tetrahydrofuranHCID 865844093(R)-arnino-N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)succinamic acid allyl ester trifluoroacetate salt

Product 1

HCID 700987653(R)-[3-[(4-cyanophenyl)acetyl]-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acid allyl ester

Reagents, catalysts & solvents 1

HCID 8900HeptaneSolvent

Procedure

As described in Example 1(c) for the preparation of N-(8-oxo-4-oxa-1,7-diaza-tricyclo[9.6.1.012,17]octadeca-11(18),12,14,16-tetraen-9-yl)-3-(3-phenyl-1-yl)succinamic acid benzyl ester, 3(R)-amino-N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)succinamic acid allyl ester trifluoroacetate salt and 3-[2-(4-cyanophenyl)-ethynyl]-2,5-dimethoxy-tetrahydrofuran were heated with trifluoroacetic acid (1 equiv) at 70° C. for 4 hours. Flash column chromatography twice with 0.5% HOAc/15% EtOAc/CH2Cl2 as eluant and azeotrope with n-heptane afforded 800 mg (36%, 43% based on recovered furan) of 3(R)-[3-[(4-cyanophenyl)acetyl]-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acid allyl ester as a brown oil. 1H NMR (CDCl3): δ 7.58 (d, 2H, J=8.1 Hz), 7.47 (dd, 1H, J=1.9, 1.9 Hz), 7.36 (d, 2H, J=8.1 Hz), 6.84 (d, 1H, J=9.0 Hz), 6.74 (dd, 1H, J=2.8, 2.8 Hz), 6.63 (dd, 1H, J=1.6, 2.8 Hz), 6.08 (dd, J=2.8, 6.8 Hz), 5.82 (ddt, 1H, J=5.9, 10.3, 17.1 Hz), 5.26 (ddd, 1H, J=1.2, 2.8, 17.1 Hz), 5.19 (q, 1H, J=7.2 Hz), 4.56 (dddd, 2H, J=1.6, 2.8, 4.4, 15.9 Hz), 4.18 (d, 1H, J=9.0 Hz), 4.05 (s, 2H), 3.34 (dd, 1H, J=7.2, 16.8 Hz), 2.99 (dd, 1H, J=7.2, 16.8 Hz), 2.72 (d, 3H, J=5.0 Hz), 0.90 (s, 9H). 13C NMR (CDCl3): δ 191.2, 170.2, 169.4, 168.0, 140.6, 132.2, 131.3, 130.3, 125.7, 125.7, 122.0, 119.0, 118.9, 110.5, 110.4, 66.0, 61.0, 59.4, 46.1, 37.5, 34.8, 31.9, 29.0, 26.5, 26.0. IR (KBr): 3320, 2965, 229, 1736, 1648, 1531, 1173 cm−1. HRFABMS: Calculated for C27H33N4O5 (M+H+): 493.2451. Found 493.2462. Anal. Calculated for C27H32N4O5•0.2 H2O•0.2 CH2Cl2: C, 63.66; H, 6.44; N, 10.92. Found: C, 63.86; H, 6.56; N, 10.58.

Sources & evidence

ORD record
ord-5d5816a6aa2c43eeb5c0dd698c936d8e
Source dataset
uspto-grants-2001_01
Patent number
US06174915B1

Reaction notes

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