Dimethylamine → HCID 73051311, compound

HRID 537280Notes

Reaction equation

HRID 537280 reaction equation
C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)[C:14]2[N:15]=[CH:16]C=CC=2N=N1.F[P-](F)(F)(F)(F)F.[F:34][C:35]1[CH:40]=[CH:39][C:38]([N:41]2[C:45]3[CH:46]=[C:47]4[C@:52]([C:54](=[O:61])[C:55]5[CH:60]=[CH:59][CH:58]=[CH:57][N:56]=5)([CH2:53][C:44]=3[CH:43]=[N:42]2)[CH2:51][N:50]([S:62]([C:65]2[CH:66]=[C:67]([CH:71]=[CH:72][CH:73]=2)[C:68]([OH:70])=O)(=[O:64])=[O:63])[CH2:49][CH2:48]4)=[CH:37][CH:36]=1.CNC.C(N(CC)CC)C>ClCCl>[F:34][C:35]1[CH:36]=[CH:37][C:38]([N:41]2[C:45]3[CH:46]=[C:47]4[C@:52]([C:54](=[O:61])[C:55]5[CH:60]=[CH:59][CH:58]=[CH:57][N:56]=5)([CH2:53][C:44]=3[CH:43]=[N:42]2)[CH2:51][N:50]([S:62]([C:65]2[CH:66]=[C:67]([CH:71]=[CH:72][CH:73]=2)[C:68]([N:15]([CH3:16])[CH3:14])=[O:70])(=[O:64])=[O:63])[CH2:49][CH2:48]4)=[CH:39][CH:40]=1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 72548447HCID 72548447, compoundHCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate Methanaminium

Product 1

HCID 73051311HCID 73051311, compoundYield 11.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate Methanaminium (HATU) (42.7 mg, 0.112 mmol) was added to a solution of (R)-3-((1-(4-fluorophenyl)-4a-picolinoyl-4a,5,7,8-tetrahydro-1H-pyrazolo[3,4-g]isoquinolin-6(4H)-yl)sulfonyl)benzoic acid (57 mg, 0.102 mmol), dimethylamine (51.0 μl, 0.102 mmol) and triethylamine (28.4 μl, 0.204 mmol) in dichloromethane (3 mL). The resultant mixture was stirred at room temperature for 1 hour. The reaction was diluted with dichloromethane (5 mL) and washed with a saturated solution of sodium hydrogen carbonate (aqueous, 5 mL). The organic phase was passed through a phase separator and solvent removed to give a yellow solid. The crude product was purified by chromatography on silica gel (gradient: 0-100% ethyl acetate in isohexane) to afford (R)-3-((1-(4-fluorophenyl)-4a-picolinoyl-4a,5,7,8-tetrahydro-1H-pyrazolo[3,4-g]isoquinolin-6(4H)-yl)sulfonyl)-N,N-dimethylbenzamide (7 mg) as a white solid. LCMS (Method F, ES-API): RT 2.24 min, m+H=586.1; 1H NMR (400 MHz, CDCl3): δ 8.68 (1H, ddd, J=4.7, 1.7, 0.9 Hz), 7.90 (1H, dt, J=7.9, 1.2 Hz), 7.84 (1H, td, J=7.7, 1.7 Hz), 7.74-7.71 (2H, m), 7.61 (1H, dt, J=7.7, 1.4 Hz), 7.57-7.39 (4H, m), 7.28 (1H, s), 7.20-7.13 (2H, m), 6.47 (1H, d, J=2.0 Hz), 5.52 (1H, dd, J=12.1, 2.0 Hz), 4.27 (1H, d, J=16.9 Hz), 3.86-3.77 (1H, m), 3.14 (3H, s), 2.94-2.76 (5H, m), 2.70 (1H, d, J=12.1 Hz), 2.50-2.43 (2H, m).

Workup

  1. washwashed with a saturated solution of sodium hydrogen carbonate (aqueous, 5 mL)
  2. customremoved
  3. customto give a yellow solid
  4. customThe crude product was purified by chromatography on silica gel (gradient: 0-100% ethyl acetate in isohexane)

Sources & evidence

ORD record
ord-d0890a97c6524822bc5836d434b86965
Source dataset
uspto-grants-2014_10
Patent number
US08859774B2

Reaction notes

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