Trifluoroacetic acid → HCID 68379418, compound

HRID 1410074Notes

Reaction equation

HRID 1410074 reaction equation
[CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:8]=[C:9]([NH:13][C:14]2[C:15]3[N:43]=[CH:42][S:41][C:16]=3[N:17]=[C:18]([C:20]3[CH:21]=[C:22]([CH:38]=[CH:39][CH:40]=3)[CH2:23][NH:24][CH:25]3[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]3)[N:19]=2)[CH:10]=[CH:11][CH:12]=1.[F:44][C:45]([F:50])([F:49])[C:46]([OH:48])=[O:47]>C(Cl)Cl>[F:44][C:45]([F:50])([F:49])[C:46]([OH:48])=[O:47].[CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:8]=[C:9]([NH:13][C:14]2[C:15]3[N:43]=[CH:42][S:41][C:16]=3[N:17]=[C:18]([C:20]3[CH:40]=[CH:39][CH:38]=[C:22]([CH2:23][NH:24][CH:25]4[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)[CH:21]=3)[N:19]=2)[CH:10]=[CH:11][CH:12]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68379371HCID 68379371, compound

Product 1

HCID 68379418HCID 68379418, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (S)-tert-butyl 4-(3-(7-(3-(2-methylpyrrolidin-1-yl)phenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzylamino)piperidine-1-carboxylate (110 mg, 0.184 mmol) in 2 mL of DCM was added 2 mL of 2,2,2-trifluoroacetic acid. The solution was stirred at room temperature overnight. The mixture was washed with NaHCO3(aq.), the organic layer was concentrated. The residue was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 ml/inj, flow rate: 20 ml/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 40% acetonitrile/60% water (0.1% TFA V/V) initially, and then proceed to 55% acetonitrile/45% water (0.1% TFA V/V) in a linear fashion after just 9 min.) to give (S)—N-(3-(2-methylpyrrolidin-1-yl)phenyl)-5-(3-((piperidin-4-ylamino)methyl)phenyl)thiazolo[5,4-d]pyrimidin-7-amine 2,2,2-trifluoroacetate (40 mg, 43%) as an oil. 1H NMR (300 MHz, DMSO): δ 9.18 (s, 1H), 8.60 (s, 1H), 8.51 (dd, 1H, J1=7.5 Hz, J2=1.2 Hz), 7.92 (s, 1H), 7.84 (brs, 1H), 7.68-7.52 (m, 3H), 7.15 (brs, 1H), 4.40 (s, 2H), 4.08-4.01 (m, 2H), 3.87-3.85 (m, 1H), 3.64-3.55 (m, 4H), 3.17-3.08 (m, 2H), 2.48-2.21 (m, 5H), 2.03-1.87 (m, 3 h), 1.34 (d, 3H, J=6.3 Hz). LC-MS: 250 [M/2+H]+, 500 [M+H]+, tR=1.20 min. HPLC: 100% at 214 nm, 100% at 254 nm, tR=4.59 min.

Workup

  1. washThe mixture was washed with NaHCO3(aq.)
  2. concentrationthe organic layer was concentrated
  3. customThe residue was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm
  4. wait40% acetonitrile/60% water (0.1% TFA V/V) initially, and then proceed to 55% acetonitrile/45% water (0.1% TFA V/V) in a linear fashion after just 9 min.

Sources & evidence

ORD record
ord-9ebcc0303b614b05a69c4c120fe0e0ee
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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