Ammonium Chloride → Taselisib

HRID 1498261Notes

Reaction equation

HRID 1498261 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[N:10]=[C:11]3[C:17]4[CH:18]=[CH:19][C:20]([C:22]5[CH:23]=[N:24][N:25]([C:27]([CH3:32])([CH3:31])[C:28](O)=[O:29])[CH:26]=5)=[CH:21][C:16]=4[O:15][CH2:14][CH2:13][N:12]3[CH:33]=2)=[N:7][C:6]([CH3:34])=[N:5]1)([CH3:3])[CH3:2].[NH4+].[Cl-].CC[N:39](C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.C(=O)(O)[O-].[Na+]>CN(C=O)C>[CH:1]([N:4]1[C:8]([C:9]2[N:10]=[C:11]3[C:17]4[CH:18]=[CH:19][C:20]([C:22]5[CH:23]=[N:24][N:25]([C:27]([CH3:32])([CH3:31])[C:28]([NH2:39])=[O:29])[CH:26]=5)=[CH:21][C:16]=4[O:15][CH2:14][CH2:13][N:12]3[CH:33]=2)=[N:7][C:6]([CH3:34])=[N:5]1)([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 582043942-(4-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanoic acid

Product 1

HCID 51001932TaselisibYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(4-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanoic acid 251 (90 mg, 0.2 mmol) was dissolved in DMF (2 mL) and treated with NH4Cl (40 mg, 0.8 mmol), DIPEA (0.3 mL, 2 mmol) followed by N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (HATU, 100 mg, 0.4 mmol). The mixture was stirred at room temperature for 2 hours. Saturated sodium bicarbonate was added, and the mixture was extracted with EtOAc. The combined organics were dried over sodium sulfate and concentrated. The crude was purified by 10% MeOH/EtOAc following by trituration with minimal EtOAc to provide 74 mg (82% yield) of 196. LC/MS (ESI+): m/z 463(M+H). 1H NMR (500 MHz, DMSO) δ 8.44-8.26 (m, 2H), 8.01 (s, 1H), 7.86 (s, 1H), 7.44 (dd, J=8.4, 1.8, 1H), 7.35 (d, J=1.7, 1H), 7.15 (s, 1H), 6.79 (s, 1H), 5.82 (dt, J=13.3, 6.6, 1H), 4.52 (s, 4H), 2.25 (s, 3H), 1.75 (s, 6H), 1.47 (d, J=6.6, 6H)

Workup

  1. extractionthe mixture was extracted with EtOAc
  2. dry with materialThe combined organics were dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe crude was purified by 10% MeOH/EtOAc following by trituration with minimal EtOAc

Sources & evidence

ORD record
ord-371cb93dd59b4c2e8229c7fbfa67fc70
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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