Homoallyl bromide → (2R,3S) N1-[(3S)-1,3-dihydro-1-methyl-2-oxo-5-phenyl-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(3-buten-1-yl)-butanediamide

HRID 2238466Notes

Reaction equation

[CH2:1](Br)[CH2:2][CH:3]=C.[CH3:6][N:7]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:10][CH:9]([NH:24][C:25](=[O:47])[C@H:26]([CH2:43][CH:44]([CH3:46])[CH3:45])[C@H:27]([CH2:40]C=C)[C:28]([NH:30]CC2C=C(F)C=C(F)C=2)=[O:29])[C:8]1=[O:48].C([O-])(=O)CCC([O-])=O.CN1C2C=CC=CC=2C(C2C=CC=CC=2)=NC(N)C1=O>>[CH3:6][N:7]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:10][C@H:9]([NH:24][C:25](=[O:47])[C@H:26]([CH2:43][CH:44]([CH3:45])[CH3:46])[C@H:27]([CH2:40][CH2:3][CH:2]=[CH2:1])[C:28]([NH2:30])=[O:29])[C:8]1=[O:48]

Participants

Reactant 4

HCID 21241Homoallyl bromide

HCID 160419Succinate

HCID 27296813-Amino-1-methyl-5-phenyl-1H-benzo[E][1,4]diazepin-2(3H)-one

HCID 9916426(2R,3S)N1-[1,3-dihydro-1-methyl-2-oxo-5-phenyl-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-allyl-N4-[3,5-difluorobenzyl]-butanediamide

Product 1

HCID 9912782(2R,3S) N1-[(3S)-1,3-dihydro-1-methyl-2-oxo-5-phenyl-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(3-buten-1-yl)-butanediamide

Procedure

A procedure analogous to the preparation of Example 5 was followed. The appropriate succinate ester was prepared using the method disclosed in PCT publication WO 98/51665), using 3-butenyl bromide for R3—X in place allyl bromide (see Scheme 2). The anti-succinate half-ester was coupled to (S)-isomer benzodiazepine (30) using the procedures of Step 1. After Steps 2 and 3, the title compound was isolated. MS (M+H)+=475.3; (M+Na)+=497.3.

Workup

customA procedure analogous to the preparation of Example 5

Sources & evidence

ORD record: ord-7b2f5e2cdf5347d699a4bf6491b0c2a7
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07718795B2

Reaction notes

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