Diisopropylethylamine → rac-[(3S,4R)-4-(4-Chloro-phenyl)-1-(5'-trifluoromethyl-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carbonyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester

HRID 527483Notes

Reaction equation

HRID 527483 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:25])[N:10]([C@H:13]2[C@H:17]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)[CH2:16][NH:15][CH2:14]2)[CH2:11][CH3:12])=[CH:4][CH:3]=1.[F:26][C:27]([F:44])([F:43])[C:28]1[CH:29]=[CH:30][C:31]([N:34]2[CH2:39][CH2:38][CH:37]([C:40](O)=[O:41])[CH2:36][CH2:35]2)=[N:32][CH:33]=1.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>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:25])[N:10]([C@H:13]2[C@H:17]([C:18]3[CH:19]=[CH:20][C:21]([Cl:24])=[CH:22][CH:23]=3)[CH2:16][N:15]([C:40]([CH:37]3[CH2:38][CH2:39][N:34]([C:31]4[CH:30]=[CH:29][C:28]([C:27]([F:44])([F:26])[F:43])=[CH:33][N:32]=4)[CH2:35][CH2:36]3)=[O:41])[CH2:14]2)[CH2:11][CH3:12])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27777881-[5-(Trifluoromethyl)pyridin-2-yl]piperidine-4-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58312626[(3S,4R)-4-(4-Chloro-phenyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester

Product 1

HCID 53245783rac-[(3S,4R)-4-(4-Chloro-phenyl)-1-(5'-trifluoromethyl-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-carbonyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl esterYield 66.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 125 mg (0.456 mmol) rac-[(3S,4R)-4-(4-Chloro-phenyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester, 198 mg (0.547 mmol) 1-(5-(trifluoromethyl)pyridin-2-yl)piperidine-4-carboxylic acid, 208 mg (0.547 mmol) HATU and 353 mg (2.73 mmol) DIPEA in 10 mL DMF and stirred for 1 h ar room temperature. The mixture was concentrated and DMF and DIPEA was added and subjected to purification by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and NEt3. The product containing fractions were evaporated to yield 187 mg (66%) of the title compound as light brown viscous oil. MS m/e: 619.4 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated
  2. additionDMF and DIPEA was added
  3. customsubjected to purification by preparative HPLC on reversed phase
  4. washeluting with a gradient
  5. customformed from acetonitrile, water and NEt3
  6. additionThe product containing fractions
  7. customwere evaporated

Sources & evidence

ORD record
ord-fa5f14d702b4412ab21057f9a2648412
Source dataset
uspto-grants-2016_05
Patent number
US09346786B2

Reaction notes

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