N-(tert-butoxycarbonyl)glycine → 1,1-dimethylethyl {2-[(2-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-indol-5-yl)amino]-2-oxoethyl}carbamate

HRID 1875028Notes

Reaction equation

HRID 1875028 reaction equation
F[P-](F)(F)(F)(F)F.[N:8]1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[Cl-].N[C:30]1[CH:38]=[C:37]2[C:33]([CH:34]=[C:35]([C:39]([NH:41][CH2:42][C:43]3[CH:48]=[CH:47][C:46]([Cl:49])=[C:45]([O:50][C:51]4[CH:56]=[C:55]([C:57]#[N:58])[CH:54]=[C:53]([Cl:59])[CH:52]=4)[C:44]=3[F:60])=[O:40])[NH:36]2)=[CH:32][CH:31]=1.[CH3:61][C:62]([O:65][C:66]([NH:68][CH2:69][C:70]([OH:72])=O)=[O:67])([CH3:64])[CH3:63].C(N(C(C)C)CC)(C)C>CN(C=O)C>[Cl:49][C:46]1[CH:47]=[CH:48][C:43]([CH2:42][NH:41][C:39]([C:35]2[NH:36][C:37]3[C:33]([CH:34]=2)=[CH:32][C:31]([NH:8][C:70](=[O:72])[CH2:69][NH:68][C:66](=[O:67])[O:65][C:62]([CH3:64])([CH3:63])[CH3:61])=[CH:30][CH:38]=3)=[O:40])=[C:44]([F:60])[C:45]=1[O:50][C:51]1[CH:56]=[C:55]([C:57]#[N:58])[CH:54]=[C:53]([Cl:59])[CH:52]=1

Participants

6

Reactant 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 594513996-Amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamideHCID 131720136BOP chloride

Product 1

HCID 866448881,1-dimethylethyl {2-[(2-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-indol-5-yl)amino]-2-oxoethyl}carbamateYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

BOP chloride (0.085 g, 0.334 mmol) was added to a solution of 6-amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide (0.065 g, 0.111 mmol), N-{[(1,1-dimethylethyl)oxy]carbonyl}glycine (0.0195 g, 0.111 mmol) and diisopropylethylamine (0.097 mL, 0.557 mmol) in DMF (1 mL). The mixture was stirred at room temperature for 1 hr, then extracted with ethyl acetate and water. The organic layer was washed with water, dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (hexane:ethyl acetate) to give the title compound (0.031 g, 80% pure). ES MS: m/z 624 (M−1).

Workup

  1. extractionextracted with ethyl acetate and water
  2. washThe organic layer was washed with water
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-deca4659167e4d0dade99cfbc98c05fc
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

Loading…