Water → HCID 178484270, compound

HRID 2278713Notes

Reaction equation

HRID 2278713 reaction equation
C(OC([NH:8][CH2:9][CH2:10][N:11]([CH2:13][C:14]1[C:15]([C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[N:30](C(OC(C)(C)C)=O)[N:29]=[CH:28]3)=[N:16][N:17](C2CCCCO2)[CH:18]=1)[CH3:12])=O)(C)(C)C.O.CC#N>O1CCCC1.Cl>[NH2:8][CH2:9][CH2:10][N:11]([CH2:13][C:14]1[C:15]([C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[NH:30][N:29]=[CH:28]3)=[N:16][NH:17][CH:18]=1)[CH3:12]

Participants

6

Reactant 3

HCID 962WaterHCID 6342Acetonitrile2×HCID 90460494HCID 90460494, compound

Product 1

HCID 178484270HCID 178484270, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (R/S) tert-butyl 5-(4-(((2-(tert-butoxycarbonylamino)ethyl)(methyl)amino)methyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)-1H-indazole-1-carboxylate (50 mg, 0.09 mmol, 1.00 equiv) in tetrahydrofuran (10 mL) and 12N hydrochloric acid (2 mL) was stirred overnight at 25° C. The resulting mixture was concentrated under vacuum to remove most of the THF. The pH value of the solution was adjusted to 9 with 10% sodium carbonate solution. The resulting mixture was concentrated under vacuum. The residue was dissolved in 5 mL of methanol and then purified by Pre-HPLC with the following conditions (1#-Pre-HPLC-005 (Waters)): Column, XBridge Shield RP18 OBD Column, 5 μm, 19×150 mm; mobile phase, water with 10 mmol NH4HCO3 and CH3CN (18% CH3CN up to 58% in 10 min, up to 95% in 1 min, down to 18% in 2 min); Detector, UV 254/220 nm to give 7 mg (29%) of (2-aminoethyl)([[3-(1H-indazol-5-yl)-1H-pyrazol-4-yl]methyl])methylamine as a white solid. 1H-NMR (300 MHz, CD3OD): δ 8.14 (s, 1H), 8.10 (s, 1H), 7.72-7.64 (m, 3H), 3.63 (s, 2H), 3.10-3.09 (m, 2H), 2.86-2.77 (m, 2H), 2.24 (s, 3H) ppm. LCMS (method A1, ESI): RT=0.78 min, m/z=271.0 [M+H]+.

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. customto remove most of the THF
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. dissolutionThe residue was dissolved in 5 mL of methanol
  5. custompurified by Pre-HPLC with the following conditions (1#-Pre-HPLC-005 (Waters))
  6. waitdown to 18% in 2 min)

Sources & evidence

ORD record
ord-8928afb187174288a32c100b5b649130
Source dataset
uspto-grants-2015_09
Patent number
US09133189B2

Reaction notes

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