Diisopropylethylamine → HCID 24797444, compound

HRID 505967Notes

Reaction equation

HRID 505967 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:8][CH2:7][CH2:6][CH2:5][C@H:4]1[OH:9].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[N:32]1[CH:37]=[C:36]([CH2:38][CH2:39][C:40]2[C:48]([C:49]3[CH:54]=[CH:53][C:52]([C:55]([F:58])([F:57])[F:56])=[CH:51][CH:50]=3)=[CH:47][C:43]([C:44](O)=[O:45])=[CH:42][N:41]=2)[CH:35]=[N:34][CH:33]=1.C(N(C(C)C)C(C)C)C>CN(C)C=O>[OH:9][C@@H:4]1[CH2:5][CH2:6][CH2:7][CH2:8][C@H:3]1[NH:2][C:44](=[O:45])[C:43]1[CH:47]=[C:48]([C:49]2[CH:50]=[CH:51][C:52]([C:55]([F:56])([F:57])[F:58])=[CH:53][CH:54]=2)[C:40]([CH2:39][CH2:38][C:36]2[CH:35]=[N:34][CH:33]=[N:32][CH:37]=2)=[N:41][CH:42]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 12228412Cyclohexanol, 2-amino-, hydrochloride (1:1), (1R,2R)-HCID 67426063HCID 67426063, compound

Product 1

HCID 24797444HCID 24797444, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of (1R,2R)-2-amino-cyclohexanol hydrochloride (41 mg, 0.27 mmol) in N,N-dimethylformamide (1.2 ml) was added to a suspension of TBTU (234 mg, 0.73 mmol), 6-(2-pyrimidin-5-yl-ethyl)-5-(4-trifluoromethyl-phenyl)-nicotinic acid (0.24 mmol) and N-ethyldiisopropylamine (0.21 ml, 1.22 mmol) in N,N-dimethylformamide (1.7 ml). The reaction mixture was shaken at room temperature for 20 hours then concentrated in vacuo. The residue was then dissolved in dichloromethane (2 ml) and washed with water (2 ml). The aqueous layer was separated and extracted with dichloromethane (2 ml), the organics were combined and the whole was dried over MgSO4 and concentrated in vacuo. The residue was purified by preparative HPLC to afford N-((1R,2R)-2-hydroxy-cyclohexyl)-6-(2-pyrimidin-5-yl-ethyl)-5-(4-trifluoromethyl-phenyl)-nicotinamide, 49 mg (44% yield over 2 steps). LC at 215 nm; Rt 3.92: 92%, m/z (ES+): 471 (M+H).

Workup

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe residue was then dissolved in dichloromethane (2 ml)
  3. washwashed with water (2 ml)
  4. customThe aqueous layer was separated
  5. extractionextracted with dichloromethane (2 ml)
  6. dry with materialthe whole was dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-ad042e9939a845caba8177910fb55561
Source dataset
uspto-grants-2010_08
Patent number
US07781593B2

Reaction notes

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