Diisopropylethylamine → tert-butyl 4-(1-(4-chlorophenyl)-2-(1H-pyrazol-1-yl)ethylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate

HRID 423104Notes

Reaction equation

HRID 423104 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:25]([O:29][C:30]([NH:32][C:33]1([C:48]([OH:50])=O)[CH2:38][CH2:37][N:36]([C:39]2[C:40]3[CH:47]=[CH:46][NH:45][C:41]=3[N:42]=[CH:43][N:44]=2)[CH2:35][CH2:34]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].[Cl:51][C:52]1[CH:57]=[CH:56][C:55]([CH:58]([NH2:65])[CH2:59][N:60]2[CH:64]=[CH:63][CH:62]=[N:61]2)=[CH:54][CH:53]=1.C(N(CC)C(C)C)(C)C>CN1CCCC1=O>[Cl:51][C:52]1[CH:57]=[CH:56][C:55]([CH:58]([NH:65][C:48]([C:33]2([NH:32][C:30](=[O:31])[O:29][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:34][CH2:35][N:36]([C:39]3[C:40]4[CH:47]=[CH:46][NH:45][C:41]=4[N:42]=[CH:43][N:44]=3)[CH2:37][CH2:38]2)=[O:50])[CH2:59][N:60]2[CH:64]=[CH:63][CH:62]=[N:61]2)=[CH:54][CH:53]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 16643583HCID 16643583, compound2×HCID 577503944-((tert-Butoxycarbonyl)amino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid2×

Product 1

HCID 57750325tert-butyl 4-(1-(4-chlorophenyl)-2-(1H-pyrazol-1-yl)ethylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamateYield 76.5%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

HATU (0.209 g, 0.55 mmol) was added in one portion to 4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid (Intermediate 1) (0.181 g, 0.50 mmol), 1-(4-chlorophenyl)-2-(1H-pyrazol-1-yl)ethanamine (Intermediate 92) (0.202 g, 0.5 mmol) and N,N-diisopropylethylamine (0.174 mL, 1.00 mmol) in N-methyl-2-pyrrolidinone (3.0 mL) at room temperature under argon. The resulting solution was stirred overnight. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml/minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford tert-butyl 4-(1-(4-chlorophenyl)-2-(1H-pyrazol-1-yl)ethylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (0.216 g, 76%) as a white crystalline solid.

Workup

  1. customThe reaction mixture was purified by preparative HPLC
  2. additionThe fractions containing the desired compound
  3. customwere evaporated to dryness

Sources & evidence

ORD record
ord-3b0722531f044c179108241aeb904df6
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

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