Sodium Bicarbonate → HCID 46215816, compound

HRID 2367296Notes

Reaction equation

HRID 2367296 reaction equation
CC([N:5]([C:9]1[C:17]2[C:12](=[CH:13][C:14]([C:18]3[CH:23]=[C:22]([N:24]4[CH2:29][C@@H:28]([C:30]([NH:32][C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=5)=[O:31])[CH2:27][CH2:26][C@H:25]4[CH3:39])[N:21]=[C:20]([NH:40][CH3:41])[N:19]=3)=[CH:15][CH:16]=2)[NH:11][N:10]=1)C(=O)[O-])(C)C.C([O-])(O)=O.[Na+]>CO.Cl.O>[NH2:5][C:9]1[C:17]2[C:12](=[CH:13][C:14]([C:18]3[N:19]=[C:20]([NH:40][CH3:41])[N:21]=[C:22]([N:24]4[C@H:25]([CH3:39])[CH2:26][CH2:27][C@H:28]([C:30]([NH:32][C:33]5[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=5)=[O:31])[CH2:29]4)[CH:23]=3)=[CH:15][CH:16]=2)[NH:11][N:10]=1

Participants

6

Reactant 2

HCID 516892Sodium BicarbonateHCID 86659179HCID 86659179, compound

Product 1

HCID 46215816HCID 46215816, compoundYield 51%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 1,1-dimethylethyl[6-(2-(methylamino)-6-{(2R,5S)-2-methyl-5-[(phenylamino)carbonyl]-1-piperidinyl}-4-pyrimidinyl)-1H-indazol-3-yl]carbamate (530 mg, 0.95 mmol) in CH3OH (15 mL) and conc. HCl (0.5 mL) was heated at 50° C. for a total of 6 hours. The residue was taken up in 5 mL of water, to which was added 5 mL of sat. NaHCO3. The resulting suspension was sonicated, and filtered. The yellow solids collected underwent purification by silica gel column chromatography using elution of gradient 1% A in CHCl3 to 60% A in CHCl3 (A was 200/800/20 CH3OH/CHCl3/NH4OH). Trituration of the residue obtained from the chromatography in MTBE (6 mL), followed by drying under vacuum at 50° C. for 20 hours afforded the title compound (221 mg) as a yellow solid. LC-MS (ES) m/z=457 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 1.33 (d, J=6.8 Hz, 3H), 1.82-1.97 (m, 3H), 2.06-2.16 (m, 1H), 2.57-2.65 (m, 1H), 2.98 (s, 3H), 3.15-3.25 (m, 1H), 6.51 (s, 1H), 7.12 (t, J=7.5 Hz, 1H), 7.34 (t, J=8.1 Hz, 2H), 7.54 (dd, J=8.5, 1.1 Hz, 1H), 7.60 (dd, J=8.6, 1.3 Hz, 2H), 7.76 (d, J=8.3 Hz, 1H), 7.87 (s, 1H).

Workup

  1. customThe resulting suspension was sonicated
  2. filtrationfiltered
  3. customThe yellow solids collected underwent
  4. custompurification by silica gel column chromatography
  5. washelution of gradient 1% A in CHCl3 to 60% A in CHCl3 (
  6. customTrituration of the residue obtained from the chromatography in MTBE (6 mL)
  7. customby drying under vacuum at 50° C. for 20 hours

Sources & evidence

ORD record
ord-05c20377afad4daba021810311d839f9
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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