Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → (R)-tert-Butyl 2-(4-((3-(dimethylamino)pyrrolidin-1-yl)methyl)benzamido)-4-(thiophen-2-yl)phenylcarbamate

HRID 1907693Notes

Reaction equation

HRID 1907693 reaction equation
[CH3:1][N:2]([CH3:18])[C@@H:3]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=2)[CH2:4]1.[NH2:19][C:20]1[CH:25]=[C:24]([C:26]2[S:27][CH:28]=[CH:29][CH:30]=2)[CH:23]=[CH:22][C:21]=1[NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35].CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>N1C=CC=CC=1>[CH3:18][N:2]([CH3:1])[C@@H:3]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([C:13]([NH:19][C:20]3[CH:25]=[C:24]([C:26]4[S:27][CH:28]=[CH:29][CH:30]=4)[CH:23]=[CH:22][C:21]=3[NH:31][C:32](=[O:38])[O:33][C:34]([CH3:36])([CH3:35])[CH3:37])=[O:15])=[CH:16][CH:17]=2)[CH2:4]1

Participants

5

Reactant 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 57717474tert-Butyl (2-amino-4-(thiophen-2-yl)phenyl)carbamateHCID 59737509(R)-4-((3-(Dimethylamino)pyrrolidin-1-yl)methyl)benzoic acid

Product 1

HCID 59737389(R)-tert-Butyl 2-(4-((3-(dimethylamino)pyrrolidin-1-yl)methyl)benzamido)-4-(thiophen-2-yl)phenylcarbamateYield 67.9%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of acid 7 (0.20 g, 0.62 mmol), amine 4 (0.164 g, 0.56 mmol) and BOP reagent (0.30 g, 0.68 mmol) in pyridine (4 mL) was stirred for 18 h, concentrated, diluted with AcOEt, washed with aqueous sodium bicarbonate (NaHCO3), brine, dried over MgSO4, filtered and concentrated. Flash chromatography purification of the residue (eluent: 1:1 MeOH:AcOEt with 1% triethylamine) gave compound 8 (0.198 g, 67% yield).

Workup

  1. concentrationconcentrated
  2. additiondiluted with AcOEt
  3. washwashed with aqueous sodium bicarbonate (NaHCO3), brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customFlash chromatography purification of the residue (eluent: 1:1 MeOH:AcOEt with 1% triethylamine)

Sources & evidence

ORD record
ord-34d6c9b10df842198a24abc601dec245
Source dataset
uspto-grants-2013_12
Patent number
US08598168B2

Reaction notes

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