Sodium Carbonate → HCID 67129991, compound

HRID 1038809Notes

Reaction equation

HRID 1038809 reaction equation
[CH:1]1([NH:4][C:5]2[C:6]3[O:26][CH:25]=[CH:24][C:7]=3[N:8]=[C:9]([NH:11][C:12]3[CH:20]=[C:19]4[C:15]([C:16]([C:21]([OH:23])=O)=[N:17][NH:18]4)=[CH:14][CH:13]=3)[N:10]=2)[CH2:3][CH2:2]1.[NH:27]1[C:35]2[C:30](=CC=C[CH:34]=2)C(C([O-])=O)=N1.C1(N)CC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C>[CH:35]1([NH:27][C:21]([C:16]2[C:15]3[C:19](=[CH:20][C:12]([NH:11][C:9]4[N:10]=[C:5]([NH:4][CH:1]5[CH2:2][CH2:3]5)[C:6]5[O:26][CH:25]=[CH:24][C:7]=5[N:8]=4)=[CH:13][CH:14]=3)[NH:18][N:17]=2)=[O:23])[CH2:34][CH2:30]1

Participants

8

Reactant 6

HCID 10340Sodium CarbonateHCID 69828Cyclopropylamine2×HCID 81531Diisopropylethylamine2×HCID 4121167HCID 4121167, compound2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 67129988HCID 67129988, compound

Product 1

HCID 67129991HCID 67129991, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-(4-(Cyclopropylamino)furo[3,2-d]pyrimidin-2-ylamino)-1H-indazole-3-carboxylic acid (0.13 g, 0.37 mmol, [prepared using I from methyl 6-nitro-1-(2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carboxylate [WO 2010/027500 page 171 intermediate 83 step A], B with Preparation #A.1, J and AI), cyclopropylamine (0.013 mL, 0.18 mmol), and HATU (0.078 g, 0.20 mmol) were combined in DMF (1.9 mL). DIEA (0.081 mL, 0.46 mmol) was added and the mixture was stirred at rt for about 18 h. Additional cyclopropylamine (0.013 mL, 0.19 mmol) was added and the mixture was stirred for about 6 h. HATU (0.04 g, 0.10 mmol) and DIEA (0.1 mL) were added and the mixture was stirred for about 24 h. A solution of 1 M aqueous Na2CO3 (5 mL) was added. The aqueous layer was separated and extracted with DCM (3×10 mL). The combined organic layers were washed with brine (5 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was dissolved in a mixture of MeOH and DCM and adsorbed onto silica gel (˜3 mL). The residue was purified by column chromatography (25 g silica gel) eluting with 2-8% MeOH in DCM to give N-cyclopropyl-6-(4-(cyclopropylamino)furo[3,2-d]pyrimidin-2-ylamino)-1H-indazole-3-carboxamide (0.052 g, 72%) as a white solid on drying under vacuum at about 40° C.: LCMS (Table 2, Method c) Rt=1.80 min.; MS m/z: 390 (M+H)+. Syk IC50=A

Workup

  1. stirringthe mixture was stirred for about 6 h
  2. stirringthe mixture was stirred for about 24 h
  3. customThe aqueous layer was separated
  4. extractionextracted with DCM (3×10 mL)
  5. washThe combined organic layers were washed with brine (5 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThe residue was dissolved in a mixture of MeOH and DCM
  10. customThe residue was purified by column chromatography (25 g silica gel)
  11. washeluting with 2-8% MeOH in DCM

Sources & evidence

ORD record
ord-02b805a33e9a407ab34e6e9ee34c2f5f
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Reaction notes

Loading…