Triethylamine → tert-butyl (2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)(6-{[(1-methylcyclopropyl)carbonyl]amino}pyridin-3-yl)carbamate

HRID 1039079Notes

Reaction equation

HRID 1039079 reaction equation
NC1C(C)=CC([N:8]([CH2:16][CH2:17][C@@H:18]2[CH2:20][C@@H:19]2[CH:21]2[CH2:26][CH2:25][N:24]([C:27]3[N:32]=[CH:31][C:30]([Cl:33])=[CH:29][N:28]=3)[CH2:23][CH2:22]2)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=NC=1.[CH3:35][C:36]1([C:39]([OH:41])=O)[CH2:38][CH2:37]1.CN(C(O[N:50]1N=N[C:52]2[CH:53]=[CH:54][CH:55]=[N:56][C:51]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C>[Cl:33][C:30]1[CH:31]=[N:32][C:27]([N:24]2[CH2:23][CH2:22][CH:21]([C@H:19]3[CH2:20][C@H:18]3[CH2:17][CH2:16][N:8]([C:54]3[CH:55]=[N:56][C:51]([NH:50][C:39]([C:36]4([CH3:35])[CH2:38][CH2:37]4)=[O:41])=[CH:52][CH:53]=3)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:26][CH2:25]2)=[N:28][CH:29]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 813261-Methylcyclopropanecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67962339tert-butyl (5-amino-4-methylpyridin-2-yl)(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)carbamate

Product 1

HCID 86666144tert-butyl (2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)(6-{[(1-methylcyclopropyl)carbonyl]amino}pyridin-3-yl)carbamate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-butyl (5-amino-4-methylpyridin-2-yl)(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)carbamate (80 mg, 0.17 mmol) from Step 2 of Example 30a, 1-methylcyclopropane-1-carboxylic acid (19.2 mg, 0.19 mmol), HATU (84 mg, 0.22 mmol) and triethylamine (68.5 mg, 0.68 mmol) were added in DMF (1.7 mL) at room temperature for 2 days. The reaction was added ethyl acetate (20 mL, washed with sodium bicarbonate saturated solution (10 mL), second wash with brine (10 mL). The organic phase was dried by magnesium sulfate, filtered, concentrated and purified by column chromatography through a 25 gram Biotage SNAP KP-Sil™ silica gel cartridge eluting with 30% ethyl acetate/hexanes to give the title compound as a pale yellow oil.

Workup

  1. washwashed with sodium bicarbonate saturated solution (10 mL)
  2. washsecond wash with brine (10 mL)
  3. dry with materialThe organic phase was dried by magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by column chromatography through a 25 gram Biotage SNAP KP-Sil™ silica gel cartridge
  7. washeluting with 30% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-64211d634c044e25816265ca9af82ce7
Source dataset
uspto-grants-2013_10
Patent number
US08552022B2

Reaction notes

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