1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-2-Amino-N-{4-[(4-methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-propionamide

HRID 1876216Notes

Reaction equation

HRID 1876216 reaction equation
C(OC(=O)[NH:7][C@H:8]([C:10](=[O:33])[NH:11][CH2:12][C:13]1[N:22]=[C:21]([N:23]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[CH3:24])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]=1)[CH3:9])(C)(C)C.NCC1N=C(N(C2C=CC(OC)=CC=2)C)C2C(=CC=CC=2)N=1.N(C(OC(C)(C)C)=O)[C@H](C(O)=O)C.CCN=C=NCCCN(C)C.C(N(C(C)C)C(C)C)C>CN(C=O)C.CCOC(C)=O>[NH2:7][C@@H:8]([CH3:9])[C:10]([NH:11][CH2:12][C:13]1[N:22]=[C:21]([N:23]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[CH3:24])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]=1)=[O:33]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 85082Tert-butoxycarbonylalanineHCID 44555457(2-Aminomethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amineHCID 59237291[(S)-1-({4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-carbamoyl)-ethyl]-carbamic acid tert-butyl ester

Product 1

HCID 59242103(S)-2-Amino-N-{4-[(4-methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-propionamideYield 83%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

[(S)-1-({4-[(4-Methoxy-phenyl)-methyl-amino]-quinazolin-2-ylmethyl}-carbamoyl)-ethyl]-carbamic acid tert-butyl ester: To (2-aminomethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine (210 mg, 0.74 mmol), Boc-L-Ala-OH (140 mg, 0.74 mmol), EDCI (170 mg, 0.89 mmol) and HOBt-hydrate (136 mg, 0.89 mmol) in DMF (3 mL) was added ethyl-diisopropyl-amine (383 μL, 2.2 mmol). The reaction was stirred at room temperature overnight, diluted with EtOAc and quenched with 10% aqueous HCl followed by saturated aqueous NaHCO3. The aqueous phase was extracted with EtOAc (4×15 mL). The combined organic phases were washed with brine, dried (MgSO4) and concentrated. Purification by gradient MPLC (0-20% MeOH/CH2Cl2 with 0.1% NH4OH) gave 285 mg (83%) of the title compound as a yellow solid. 1H NMR (MeOH-d4) δ 7.69 (d, 1H), 7.61-7.57 (m, 1H), 7.1 (d, 2H), 7.03-6.98 (m, 4H), 4.61-4.49 (m, 2H), 4.23 (q, 1H), 3.83 (s, 3H), 3.62 (s, 3H), 1.44 (s, 9H), 1.4 (d, 3H); LC-MS (ESI+; 466 ([M+H]+)).

Workup

  1. customquenched with 10% aqueous HCl
  2. extractionThe aqueous phase was extracted with EtOAc (4×15 mL)
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customPurification by gradient MPLC (0-20% MeOH/CH2Cl2 with 0.1% NH4OH)

Sources & evidence

ORD record
ord-2c5b702b64fb4e639dcde21c255efe7a
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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