1-Hydroxybenzotriazole → 2-[5-benzyloxycarbonylamino-2-(4-fluorophenyl)-6-oxo-1,6-dihydro-1-pyrimidinyl]-N-[1(S)-benzyl-3,3-difluoro-2-oxo-3-[N-(benzyl)carbamoyl]propyl]acetamide

HRID 617651Notes

Reaction equation

HRID 617651 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:17](=[O:18])[N:16]([CH2:19][C:20](O)=[O:21])[C:15]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)=[N:14][CH:13]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:30][C@@H:31]([CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[C@@H:32]([OH:46])[C:33]([F:45])([F:44])[C:34]([NH:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:35].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>ClCCl>[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:17](=[O:18])[N:16]([CH2:19][C:20]([NH:30][C@@H:31]([CH2:47][C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)[C:32](=[O:46])[C:33]([F:45])([F:44])[C:34](=[O:35])[NH:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[O:21])[C:15]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)=[N:14][CH:13]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10023705HCID 10023705, compoundHCID 18391679N-[4(S)-amino-2,2-difluoro-3(R)-hydroxy-5-phenylpentanoyl]benzylamine

Product 1

HCID 154353052-[5-benzyloxycarbonylamino-2-(4-fluorophenyl)-6-oxo-1,6-dihydro-1-pyrimidinyl]-N-[1(S)-benzyl-3,3-difluoro-2-oxo-3-[N-(benzyl)carbamoyl]propyl]acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-[5-Benzyloxycarbonylamino-2-(4-fluorophenyl)-6-oxo-1,6-dihydro-1-pyrimidinyl]-N-[1(S)-benzyl-3,3-difluoro-2(R)-hydroxy-3-[N-(benzyl)caramoyl]propyl]acetamide was synthesized in the same manner as in Example 1. That is, 2-[5-benzyloxycarbonylamino-2-(4-fluorophenyl)-6-oxo-1,6-dihydro-1-pyrimidinyl]acetic acid (title compound in Reference Example 3, mixture with benzyl alcohol, 380 mg, 0.897 mmol) was treated with N-[4(S)-amino-2,2-difluoro-3(R)-hydroxy-5-phenylpentanoyl]benzylamine (title compound in Reference Example 6: 300 mg, 0.897 mmol), HOBT (242 mg, 1.79 mmol) and WSCI hydrochloride (206 mg, 1.08 mmol) in dichloromethane (30 mL) to give 590 mg (92%) of the target compound as colorless crystals.

Workup

  1. custom2-[5-Benzyloxycarbonylamino-2-(4-fluorophenyl)-6-oxo-1,6-dihydro-1-pyrimidinyl]-N-[1(S)-benzyl-3,3-difluoro-2(R)-hydroxy-3-[N-(benzyl)caramoyl]propyl]acetamide was synthesized in the same manner as in Example 1

Sources & evidence

ORD record
ord-335bcf61fd8143c0be27ebfff52a966a
Source dataset
uspto-grants-1999_09
Patent number
US05948785

Reaction notes

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