Aluminium lithium hydride → HCID 57378748, compound

HRID 877068Notes

Reaction equation

HRID 877068 reaction equation
C[O:2][C:3]([C:5]1[C:13]2[C:9](=[C:10]3[N:17]=[C:16]([C:18]4[CH:23]=[CH:22][C:21]([C:24]5([NH:28]C(OC(C)(C)C)=O)[CH2:27][CH2:26][CH2:25]5)=[CH:20][CH:19]=4)[C:15]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[CH:14][N:11]3[N:12]=2)[CH:8]=[CH:7][CH:6]=1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].C(OC(=O)NC1(C2C=CC(C3C(C4C=CC=CC=4)=CN4N=C5C(C=CC=C5CO)=C4N=3)=CC=2)CCC1)(C)(C)C>O1CCCC1.Cl.O1CCOCC1>[NH2:28][C:24]1([C:21]2[CH:20]=[CH:19][C:18]([C:16]3[C:15]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)=[CH:14][N:11]4[N:12]=[C:13]5[C:9]([CH:8]=[CH:7][CH:6]=[C:5]5[CH2:3][OH:2])=[C:10]4[N:17]=3)=[CH:23][CH:22]=2)[CH2:25][CH2:26][CH2:27]1

Participants

7

Reactant 3

HCID 21226445Aluminium lithium hydride3×HCID 86702542HCID 86702542, compoundHCID 86702543HCID 86702543, compound

Product 1

HCID 57378748HCID 57378748, compoundYield 2.2%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

135.7 mg (0.247 mmol) 2-[4-(tert-Butoxycarbonylaminocyclobutyl)phenyl]-3-phenylpyrimido[1,2-b]indazole-7-carboxylic acid methyl ester, described in example 10, were dissolved in 5 mL tetrahydrofuran. After addition of 18.8 mg (0.5 mmol) lithium aluminium hydride at −78° C., the reaction mixture was stirred was four hours. After addition of another equivalent lithium aluminium hydride stirring was continued for three hours at ° C. Stirring was further continued over night at room temperature. Additional four equivalents lithium aluminium hydride were added and the reaction mixture was stirred for 24 hours at room temperature. 96 mg {1-[4-(7-Hydroxymethyl-3-phenylpyrimido[1,2-b]indazol-2-yl)phenyl]-cyclobutyl}carbamic acid tert-butylester were stirred over night in 6 mL 4M hydrogen chloride in dioxane. The solvent was evaporated and the residue was treated with saturated sodium bicarbonate. After extraction with dichloromethane (trice) the combined organic phases were washed with brine, dried and filtrated. The solvent was evaporated and the residue was purified by HPLC yielding 2.3 mg of the title compound.

Workup

  1. waitwas continued for three hours at ° C
  2. stirringStirring
  3. waitwas further continued over night at room temperature
  4. stirringthe reaction mixture was stirred for 24 hours at room temperature
  5. customThe solvent was evaporated
  6. additionthe residue was treated with saturated sodium bicarbonate
  7. extractionAfter extraction with dichloromethane (trice) the combined organic phases
  8. washwere washed with brine
  9. customdried
  10. filtrationfiltrated
  11. customThe solvent was evaporated
  12. customthe residue was purified by HPLC

Sources & evidence

ORD record
ord-417b8582beea47088200b22abc423a29
Source dataset
uspto-grants-2015_03
Patent number
US08987286B2

Reaction notes

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