3-Aminophenylboronic acid → 6-[3-[(4,5-dihydro-1H-imidazol-2-yl)amino]phenyl]-(alphaS)-3,4-dihydro-4-oxo-alpha-[[(phenylmethoxy)carbonyl]amino]-2-quinazolinepropanoic Acid

HRID 1793410Notes

Reaction equation

HRID 1793410 reaction equation
[NH:1]1[CH2:5][CH2:4][N:3]=[C:2]1[NH:6][CH2:7]/[CH:8]=[CH:9]/[C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[N:16]=[C:15]([CH2:20][C@H:21]([NH:25]S(C1C(C)=C(C)C(C)=C(C)C=1C)(=O)=O)[C:22]([OH:24])=[O:23])[NH:14][C:13]2=[O:40].C(OC(=O)[C@H](CC(=O)N)N[C:49]([O:51][CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)=[O:50])(C)(C)C.N[C:65]1[CH:66]=C(B(O)O)C=C[CH:70]=1.NC1NCCN=1>>[NH:1]1[CH2:5][CH2:4][N:3]=[C:2]1[NH:6][C:7]1[CH:8]=[C:9]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]=[C:15]([CH2:20][C@H:21]([NH:25][C:49]([O:51][CH2:52][C:53]2[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=2)=[O:50])[C:22]([OH:24])=[O:23])[NH:14][C:13]3=[O:40])[CH:70]=[CH:65][CH:66]=1

Participants

5

Reactant 4

HCID 922693-Aminophenylboronic acidHCID 1347844,5-Dihydro-1H-imidazol-2-amineHCID 7015714Z-Asn-OtBuHCID 1354158916-[(1E)-3-[(4,5-dihydro-1H-imidazol-2-yl)amino]-1-propenyl]-(alphaS)-3,4-dihydro-4-oxo-alpha-[[(2,3,4,5,6-pentamethylphenyl)sulfonyl]amino]-2-quinazolinepropanoic Acid

Product 1

HCID 1355307126-[3-[(4,5-dihydro-1H-imidazol-2-yl)amino]phenyl]-(alphaS)-3,4-dihydro-4-oxo-alpha-[[(phenylmethoxy)carbonyl]amino]-2-quinazolinepropanoic Acid

Procedure

Compound 9 was prepared as described for Compound 1, but instead of Compound AA2, N-carbobenzyloxyasparagine tert-butyl ester (8.2 g) was reacted with Compound AA3 and produced Compound AC1. Scheme AC shows the Suzuki cross coupling of Compound AC1 with 3-aminophenylboronic acid to produce Compound AC2. As shown in the illustration for Scheme AA, intermediate Compound AC2 (0.19 g) was converted to the corresponding 2-aminoimidazoline by coupling with Compound AA5 followed by hydrolysis to yield Compound 9. Compound 9 was isolated as a white solid (TFA salt): 1H NMR (DMSO, d6) δ 3.0 (m, 1 H), 3.2 (m, 1 H), 3.4 (m, 2 H), 3.6 (s, 4H), 4.7 (m, 1 H), 5.0 (s, 2 H), 7.0 (m, 1 H), 7.3 (m, 5 H), 7.5 (m, 2 H), 7.7 (d, J=8 Hz, 1 H), 7.8 (d, J=8 Hz, 1 H), 8.1 (d, J=8 Hz, 1 H), 8.3 (s, 1 H); MS m/e 527 (MH+).

Workup

  1. customCompound 9 was prepared
  2. customproduced Compound AC1
  3. customto produce Compound AC2
  4. customfollowed by hydrolysis

Sources & evidence

ORD record
ord-f38f20fcd11c428d8403f2228fd873dd
Source dataset
uspto-grants-2006_07
Patent number
US07081460B2

Reaction notes

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