Acetic Acid → HCID 118522337, compound

HRID 529772Notes

Reaction equation

HRID 529772 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:32][CH:33]([F:35])[F:34])=[C:6]([C:8]2[N:9]=[C:10]([N:25]3[CH2:30][CH2:29][C:28](=O)[CH2:27][CH2:26]3)[S:11][C:12]=2[NH:13][C:14]([C:16]2[CH:17]=[N:18][N:19]3[CH:24]=[CH:23][CH:22]=[N:21][C:20]=23)=[O:15])[CH:7]=1.[CH3:36][NH:37][CH2:38][CH2:39][C:40]#[N:41].C(O)(=O)C.C([BH3-])#N>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:32][CH:33]([F:35])[F:34])=[C:6]([C:8]2[N:9]=[C:10]([N:25]3[CH2:26][CH2:27][CH:28]([N:37]([CH2:38][CH2:39][C:40]#[N:41])[CH3:36])[CH2:29][CH2:30]3)[S:11][C:12]=2[NH:13][C:14]([C:16]2[CH:17]=[N:18][N:19]3[CH:24]=[CH:23][CH:22]=[N:21][C:20]=23)=[O:15])[CH:7]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 69656Propanenitrile, 3-(methylamino)-HCID 498716Cyano-borohydrideHCID 131735628HCID 131735628, compound

Product 1

HCID 118522337HCID 118522337, compoundYield 46.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent4×HCID 6344DichloromethaneSolvent

Procedure

Pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [4-(5-chloro-2-difluoromethoxy-phenyl)-2-(4-oxo-piperidin-1-yl)-thiazol-5-yl]-amide (90 mg, 0.17 mmol) was dissolved in DCM (2 ml) and N-methyl-β-alaninenitrile (20 μl, 0.21 mmol), acetic acid (200 μl) and macroporous polymer supported cyanoborohydride (166 mg, 0.36 mmol) were successively added and stirred at room temperature for 16 hours. The mixture was diluted with MeOH and loaded onto an SCX-2 cartridge which had been conditioned with MeOH. After flushing with MeOH, the product was eluted with 2M ammonia in MeOH. The resulting yellow glass was purified by MDAP (Method 1). Appropriate fractions were combined and evaporated to afford a yellow glass. The residue was dissolved in MeOH and loaded onto an SCX-2 cartridge which had been conditioned with MeOH. After flushing with MeOH, the product was eluted with 2M ammonia in MeOH to give the title compound as a yellow solid (46 mg, 46%). LCMS (Method 5) [M+H]+=587.2, RT=3.19 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 10.23 (s, 1H), 9.36 (dd, 1H, J=1.6, 7.0 Hz), 8.68 (s, 1H), 8.64 (dd, 1H, J=1.6, 4.3 Hz), 7.67 (d, 1H, J=2.6 Hz), 7.59 (dd, 1H, J=2.7, 8.9 Hz), 7.41 (d, 1H, J=8.6 Hz), 7.31 (dd, 1H, J=4.3, 7.1 Hz), 7.18 (t, 1H, J=73.9 Hz), 3.94 (d, 2H, J=12.8 Hz), 3.04-2.96 (m, 2H), 2.72-2.60 (m, 5H), 2.24 (s, 3H), 1.79 (d, 2H, J=10.9 Hz), 1.59-1.47 (m, 2H).

Workup

  1. additionwere successively added
  2. customAfter flushing with MeOH
  3. washthe product was eluted with 2M ammonia in MeOH
  4. customThe resulting yellow glass was purified by MDAP (Method 1)
  5. customevaporated
  6. customto afford a yellow glass
  7. customAfter flushing with MeOH
  8. washthe product was eluted with 2M ammonia in MeOH

Sources & evidence

ORD record
ord-cc7d139d4e6d4846b65087dfc074fed6
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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