Diisopropylethylamine → 3-({[5-[(tert-Butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazol-4-yl]carbonyl}amino)-4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate

HRID 1499451Notes

Reaction equation

HRID 1499451 reaction equation
[C:1]([O:4][CH:5]1[C:9]2=[N:10][CH:11]=[C:12]([NH2:28])[C:13]([N:14]3[CH2:19][CH2:18][CH2:17][C@H:16]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:15]3)=[C:8]2[CH2:7][CH2:6]1)(=[O:3])[CH3:2].[C:29]([O:33][C:34]([NH:36][C:37]1[S:41][C:40]([C:42]2[C:47]([F:48])=[CH:46][CH:45]=[CH:44][C:43]=2[F:49])=[N:39][C:38]=1[C:50](O)=[O:51])=[O:35])([CH3:32])([CH3:31])[CH3:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([O:4][CH:5]1[C:9]2=[N:10][CH:11]=[C:12]([NH:28][C:50]([C:38]3[N:39]=[C:40]([C:42]4[C:47]([F:48])=[CH:46][CH:45]=[CH:44][C:43]=4[F:49])[S:41][C:37]=3[NH:36][C:34]([O:33][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:35])=[O:51])[C:13]([N:14]3[CH2:19][CH2:18][CH2:17][C@H:16]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:15]3)=[C:8]2[CH2:7][CH2:6]1)(=[O:3])[CH3:2]

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 674381985-((Tert-butoxycarbonyl)amino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acidHCID 867266943-Amino-4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate

Product 1

HCID 867266953-({[5-[(tert-Butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazol-4-yl]carbonyl}amino)-4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetateYield 80.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-Amino-4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate (20 mg, 0.051 mmol), (5-[(tert-butoxycarbonyl)amino]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxylic acid (Example 1, step 6, 22 mg, 0.062 mmol), HATU (49 mg, 0.13 mmol), DMF (0.12 mL) and DIPEA (20 mg, 0.15 mmol) were mixed together and stirred at room temperature for 16 h. The mixture was concentrated under reduced pressure and purified by silica gel column chromatography (eluting with 0-100% EtOAc in hexanes) to give the sub-title compound as a colorless gum (30 mg, 80%). LCMS calc. for C35H43F2N6O7S (M+H)+: m/z=729.3. Found: 729.1.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. custompurified by silica gel column chromatography (eluting with 0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-33bbdad8ebc44f729b20fbdc91f9c07f
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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