Diisopropylethylamine → HCID 131736365, compound

HRID 1055464Notes

Reaction equation

HRID 1055464 reaction equation
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:28][C@H:29]1[CH2:35][O:34][C:33]2[CH:36]=[CH:37][CH:38]=[CH:39][C:32]=2[N:31]([CH2:40][C:41]2[C:49]3[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=3)[N:43]([C:50]3[CH:57]=[CH:56][CH:55]=[CH:54][C:51]=3[C:52]#[N:53])[N:42]=2)[C:30]1=[O:58].[C:59]([O:63][C:64]([NH:66][C@@H:67]([CH3:71])[C:68](O)=[O:69])=[O:65])([CH3:62])([CH3:61])[CH3:60].CCN(C(C)C)C(C)C>C1COCC1.[Cl-].[Na+].O>[C:52]([C:51]1[CH:54]=[CH:55][CH:56]=[CH:57][C:50]=1[N:43]1[C:44]2[C:49](=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:41]([CH2:40][N:31]2[C:30](=[O:58])[C@@H:29]([NH:28][C:68](=[O:69])[C@@H:67]([NH:66][C:64](=[O:65])[O:63][C:59]([CH3:61])([CH3:60])[CH3:62])[CH3:71])[CH2:35][O:34][C:33]3[CH:36]=[CH:37][CH:38]=[CH:39][C:32]2=3)=[N:42]1)#[N:53]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 85082Tert-butoxycarbonylalanineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 90037102HCID 90037102, compound

Product 1

HCID 131736365HCID 131736365, compoundYield 89.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

(Benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP, 486 mg, 1.1 mmol, Eq: 1.5) was added to a mixture of (S)-2-(3-((3-amino-4-oxo-3,4-dihydrobenzo[b][1,4]oxazepin-5(2H)-yl)methyl)-1H-indazol-1-yl)benzonitrile (300 mg, 733 μmol, Eq: 1.00), (S)-2-(tert-butoxycarbonylamino)propanoic acid (208 mg, 1.1 mmol, Eq: 1.5) and DIEA (284 mg, 383 μl, 2.2 mmol, Eq: 3) in THF (10.0 mL) and the mixture was stirred at RT overnight. The mixture was diluted with brine and extracted with EtOAc, then the combined extracts were dried over Na2SO4. The mixture was filtered, concentrated and the residue was purified by silica gel chromatographyto give tert-butyl (S)-1-((S)-5-((1-(2-cyanophenyl)-1H-indazol-3-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-yl amino)-1-oxopropan-2-ylcarbamate (380 mg, 89%).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialthe combined extracts were dried over Na2SO4
  3. filtrationThe mixture was filtered
  4. concentrationconcentrated
  5. customthe residue was purified by silica gel chromatographyto

Sources & evidence

ORD record
ord-0da7272f92be4c22a0f6cad15f8ca6d9
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

Loading…