Tris(hydroxymethyl)aminomethane → HCID 73504794, compound

HRID 590807Notes

Reaction equation

HRID 590807 reaction equation
[CH2:1]([S:3](Cl)(=[O:5])=[O:4])[CH3:2].[NH2:7][C:8]1[C:12]2[CH:13]=[N:14][C:15]([NH:17][C:18]([NH:20][C@@H:21]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH3:22])=[O:19])=[CH:16][C:11]=2[N:10](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[N:9]=1.C(O)C(N)(CO)CO.C([SiH](CC)CC)C>C(Cl)Cl.N1C=CC=CC=1>[C:23]1([C@H:21]([NH:20][C:18](=[O:19])[NH:17][C:15]2[N:14]=[CH:13][C:12]3[C:8]([NH:7][S:3]([CH2:1][CH3:2])(=[O:5])=[O:4])=[N:9][NH:10][C:11]=3[CH:16]=2)[CH3:22])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 11667Ethanesulfonyl chlorideHCID 12052TriethylsilaneHCID 118271680HCID 118271680, compound

Product 1

HCID 73504794HCID 73504794, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To an 8 mL vial charged with ethanesulfonyl chloride (10.53 μL, 0.111 mmol) was added (R)-1-(3-amino-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (Example 47, Step 1; 20 mg, 0.037 mmol) in DCM (1 mL) and pyridine (0.1 mL). The reaction mixture was stirred at room temperature for 2 h. Excess sulfonyl chloride was quenched by shaking with MP-Trisamine (91 mg, 0.186 mmol) for 3 h. The resin was filtered, the volatiles removed in vacuo, and the resulting residue dissolved in TFA (1 mL) and stirred at room temperature for 1 h. Triethylsilane (5.93 μL, 0.037 mmol) was added and the reaction mixture was stirred for an additional 5 min. The reaction mixture was concentrated in vacuo, the resulting crude residue dissolved in DMSO (1.5 mL), filtered, and purified by mass-triggered reverse phase HPLC to afford (R)—N-(6-(3-(1-phenylethyl)ureido)-1H-pyrazolo[4,3-c]pyridin-3-yl)ethanesulfonamide. MS ESI calc'd. For C17H20N6O3S [M+1]+ 389. found 389. 1H NMR (500 MHz, DMSO-d6) δ 12.74 (1H, s), 10.63 (1H, s), 9.20 (1H, s), 8.76 (1H, s), 7.70 (1H, s), 7.50 (1H, s), 7.31 (4H, d, J=4.4 Hz), 7.20-7.21 (1H, m), 4.84 (1H, t, J=7.2 Hz), 3.30 (2H, q, J=7.4 Hz), 1.38 (3H, d, J=7.0 Hz), 1.23 (3H, t, J=7.4 Hz).

Workup

  1. customExcess sulfonyl chloride was quenched
  2. filtrationThe resin was filtered
  3. customthe volatiles removed in vacuo
  4. dissolutionthe resulting residue dissolved in TFA (1 mL)
  5. stirringstirred at room temperature for 1 h
  6. stirringthe reaction mixture was stirred for an additional 5 min
  7. concentrationThe reaction mixture was concentrated in vacuo
  8. dissolutionthe resulting crude residue dissolved in DMSO (1.5 mL)
  9. filtrationfiltered
  10. custompurified by mass-triggered reverse phase HPLC

Sources & evidence

ORD record
ord-d610420ccb034edba5d496a050f4c4cf
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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