Diisopropylethylamine → Tert-butyl 3-(4-(4-cyano-2-(2,6-difluorophenyl)oxazol-5-ylamino)phenylamino)-3-oxopropyl(methyl)carbamate

HRID 715016Notes

Reaction equation

HRID 715016 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:14])[CH2:9][CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.[NH2:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32]2[O:36][C:35]([C:37]3[C:42]([F:43])=[CH:41][CH:40]=[CH:39][C:38]=3[F:44])=[N:34][C:33]=2[C:45]#[N:46])=[CH:27][CH:26]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C=O)C>[C:45]([C:33]1[N:34]=[C:35]([C:37]2[C:38]([F:44])=[CH:39][CH:40]=[CH:41][C:42]=2[F:43])[O:36][C:32]=1[NH:31][C:28]1[CH:27]=[CH:26][C:25]([NH:24][C:11](=[O:13])[CH2:10][CH2:9][N:8]([CH3:14])[C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:30][CH:29]=1)#[N:46]

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 27609523-(Methylamino)propanoic acid, N-BOC protected2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595874505-(4-Aminophenylamino)-2-(2,6-difluorophenyl)oxazole-4-carbonitrile

Product 1

HCID 59587674Tert-butyl 3-(4-(4-cyano-2-(2,6-difluorophenyl)oxazol-5-ylamino)phenylamino)-3-oxopropyl(methyl)carbamateYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-(tert-butoxycarbonyl)-3-methylaminopropanoic acid (0.022 g, 0.11 mmol) in DMF (1.25 ml) were added O-(7-azabenzotriazol-1-yl)-N,N,N′,N1-tetramethyluronium hexafluorophosphate (0.040 g, 0.11 mmol) and diisopropylethylamine (0.018 ml, 0.11 mmol) followed by 5-(4-aminophenylamino)-2-(2,6-difluorophenyl)oxazole-4-carbonitrile (0.030 g, 0.10 mmol) and the resultant mixture stirred at room temperature overnight. A further portion of N-(tert-butoxycarbonyl)-3-methylaminopropanoic acid (0.022 g, 0.11 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.040 g, 0.11 mmol) and diisopropylethylamine (0.018 ml, 0.11 mmol) was added and the reaction stirred for 2 hours at room temperature. The solvent was removed in vacuo and the residue purified by preparative HPLC to afford tert-butyl 3-(4-(4-cyano-2-(2,6-difluorophenyl)oxazol-5-ylamino)phenylamino)-3-oxopropyl(methyl)carbamate (0.021 g, 0.04 mmol, 44%) as a white solid. LCMS (2) Rt: 3.03 min; m/z (ES+) 498.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue purified by preparative HPLC

Sources & evidence

ORD record
ord-76ce27d6854a488ab4c17244680b14f5
Source dataset
uspto-grants-2015_11
Patent number
US09187465B2

Reaction notes

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