2-(4-(Hydroxymethyl)-1H-indol-1-yl)benzonitrile → (S)-N-((S)-5-((1-(2-Cyanophenyl)-1H-indol-4-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-yl)-2-(methylamino)propanamide

HRID 1055459Notes

Reaction equation

C[N:2]([C@@H:10]([CH3:26])[C:11](=[O:25])[NH:12][C@H:13]1[CH2:19][O:18][C:17]2[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=2[NH:15][C:14]1=[O:24])[C:3](=O)OC(C)(C)C.O[CH2:28][C:29]1[CH:37]=[CH:36][CH:35]=[C:34]2[C:30]=1[CH:31]=[CH:32][N:33]2[C:38]1[CH:45]=[CH:44][CH:43]=[CH:42][C:39]=1[C:40]#[N:41]>>[C:40]([C:39]1[CH:42]=[CH:43][CH:44]=[CH:45][C:38]=1[N:33]1[C:34]2[C:30](=[C:29]([CH2:28][N:15]3[C:14](=[O:24])[C@@H:13]([NH:12][C:11](=[O:25])[C@@H:10]([NH:2][CH3:3])[CH3:26])[CH2:19][O:18][C:17]4[CH:20]=[CH:21][CH:22]=[CH:23][C:16]3=4)[CH:37]=[CH:36][CH:35]=2)[CH:31]=[CH:32]1)#[N:41]

Participants

Reactant 2

HCID 189504042-(4-(Hydroxymethyl)-1H-indol-1-yl)benzonitrile

HCID 72713380tert-Butyl methyl((S)-1-oxo-1-((S)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)propan-2-yl)carbamate

Product 1

HCID 73055138(S)-N-((S)-5-((1-(2-Cyanophenyl)-1H-indol-4-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-yl)-2-(methylamino)propanamideYield 10.3%

Conditions

Temperature: 60 °C

Procedure

In a similar manner to that described for Example 57 except in Step 1 the mixture was heated at 60° C. for 2.5 d and in Step 2 the material was purified by silica gel chromatography, tert-butyl methyl((S)-1-oxo-1-((S)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino) propan-2-yl)carbamate (250 mg, 688 μmol, Eq: 1.00), 2-(4-(hydroxymethyl)-1H-indol-1-yl)benzonitrile (440 mg, 1.77 mmol, Eq: 2.58) was converted to the title compound (35 mg) as a white solid. MS m/z 494 (MH+)

Sources & evidence

ORD record: ord-33f3f2b4c255446d999e3b4ab2804e1f
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394263B2

Reaction notes

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