(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acid → ((S)-1-{(S)-1-[1-(2-Cyano-phenyl)-1H-indazol-3-ylmethyl]-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl}-ethyl)-methyl-carbamic acid tert-butyl ester

HRID 1481904Notes

Reaction equation

HRID 1481904 reaction equation
[C:1]([O:5][C:6](=[O:40])[N:7]([C@H:9]([C:11](=[O:39])[NH:12][C@@H:13]1[C:19](=[O:20])[N:18]([CH2:21][C:22]2C3C(=C(Br)C=CC=3)C=[CH:24][C:23]=2OC)[C:17]2[CH:35]=[CH:36][CH:37]=[CH:38][C:16]=2[NH:15][CH2:14]1)[CH3:10])[CH3:8])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.N[C@@H]1C(=O)N(CC2C3[C:61](=[CH:62][CH:63]=[CH:64]C=3)[N:60]([C:67]3[CH:74]=[CH:73][CH:72]=[CH:71][C:68]=3[C:69]#[N:70])[N:59]=2)C2C=CC=CC=2NC1.N(C(OC(C)(C)C)=O)(C)[C@H](C(O)=O)C>>[C:1]([O:5][C:6](=[O:40])[N:7]([C@H:9]([C:11](=[O:39])[NH:12][C@@H:13]1[C:19](=[O:20])[N:18]([CH2:21][C:22]2[C:23]3[C:61](=[CH:62][CH:63]=[CH:64][CH:24]=3)[N:60]([C:67]3[CH:74]=[CH:73][CH:72]=[CH:71][C:68]=3[C:69]#[N:70])[N:59]=2)[C:17]2[CH:35]=[CH:36][CH:37]=[CH:38][C:16]=2[NH:15][CH2:14]1)[CH3:10])[CH3:8])([CH3:2])([CH3:4])[CH3:3]

Participants

4

Reactant 3

HCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 902203652-[3-((S)-3-amino-2-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-ylmethyl)-indazol-1-yl]-benzonitrile trifluoroacetateHCID 90220831{(S)-1-[(S)-1-(5-Bromo-2-methoxy-naphthalen-1-ylmethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester2×

Product 1

HCID 90220958((S)-1-{(S)-1-[1-(2-Cyano-phenyl)-1H-indazol-3-ylmethyl]-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl}-ethyl)-methyl-carbamic acid tert-butyl esterYield 72.8%

Procedure

In a similar manner to that described for the preparation of {(S)-1-[(S)-1-(5-bromo-2-methoxy-naphthalen-1-ylmethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester (Intermediate 12), 2-[3-((S)-3-amino-2-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-ylmethyl)-indazol-1-yl]-benzonitrile trifluoroacetate (step 1 above) (680 mg, 1.30 mmol) and Boc-N-Me-Ala-OH (290.88 mg, 1.43 mmol) were converted to the title compound (570 mg, 72.8%) obtained as white solid. LC-MS: 594 (M+H).

Sources & evidence

ORD record
ord-18b3d9d10fb0473ea6624ada7f463489
Source dataset
uspto-grants-2016_08
Patent number
US09409888B2

Reaction notes

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