Tris(hydroxymethyl)aminomethane → HCID 118272478, compound

HRID 590855Notes

Reaction equation

HRID 590855 reaction equation
[NH2:1][C:2]1[C:6]2[CH:7]=[N:8][C:9]([NH:11][C:12]([NH:14][C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:16])=[O:13])=[CH:10][C:5]=2[N:4]([C:23]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:3]=1.[CH2:42]([N:44]=[C:45]=[O:46])[CH3:43].CCN(C(C)C)C(C)C.[N-]=C=O.C(O)C(N)(CO)CO>C(Cl)Cl>[CH2:42]([NH:44][C:45](=[O:46])[NH:1][C:2]1[C:6]2[CH:7]=[N:8][C:9]([NH:11][C:12]([NH:14][C@@H:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:16])=[O:13])=[CH:10][C:5]=2[N:4]([C:23]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:3]=1)[CH3:43]

Participants

7

Reactant 5

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 8022Ethyl isocyanateHCID 81531DiisopropylethylamineHCID 105034Isocyanate2×HCID 118271680HCID 118271680, compound

Product 1

HCID 118272478HCID 118272478, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an 8 mL vial charged with (R)-1-(3-amino-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (25 mg, 0.046 mmol) in DCM (1 ml) was added ethyl isocyanate (5.51 μl, 0.070 mmol) and DIEA (0.024 ml, 0.139 mmol). The vial was capped and the contents stirred at room temperature for 16 h. The course of reaction was followed by LCMS analysis. Only minor product formation was observed. Excess isocyanate (1.5 eq) was added and the reaction mixture heated to 40° C. for a further 16 h. Unreacted isocyanate was quenched by adding MP-Trisamine (229 mg, 0.464 mmol) and tumbling the vial for 3 h. The resin was filtered and the volatiles removed in vacuo to afford crude (R)-1-(3-(3-ethylureido)-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea which was taken forward without purification. MS ESI calc'd. For C37H36N7O2 [M+H]+ 610. found 610.

Workup

  1. customThe vial was capped
  2. customThe course of reaction
  3. temperaturethe reaction mixture heated to 40° C. for a further 16 h
  4. customwas quenched
  5. customvial for 3 h
  6. filtrationThe resin was filtered
  7. customthe volatiles removed in vacuo

Sources & evidence

ORD record
ord-0022906ccf844456ba16e150f6be480a
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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