Water → HCID 67064746, compound

HRID 1409239Notes

Reaction equation

HRID 1409239 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[N:13]3[N:14]=[CH:15][CH:16]=[C:12]3[N:11]=[C:10]([NH:17][C:18](=[O:29])[C:19]3[CH:24]=[CH:23][C:22]([C:25]([OH:28])([CH3:27])[CH3:26])=[CH:21][CH:20]=3)[CH:9]=2)[CH2:3]1.F[C:31](F)(F)[C:32]([O-])=[O:33].C(Cl)(=O)C.O>N1C=CC=CC=1>[C:32]([NH:1][C@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[N:13]3[N:14]=[CH:15][CH:16]=[C:12]3[N:11]=[C:10]([NH:17][C:18](=[O:29])[C:19]3[CH:24]=[CH:23][C:22]([C:25]([OH:28])([CH3:26])[CH3:27])=[CH:21][CH:20]=3)[CH:9]=2)[CH2:3]1)(=[O:33])[CH3:31]

Participants

6

Reactant 4

HCID 962WaterHCID 6367Acetyl chloride2×HCID 84468TrifluoroacetateHCID 67063732HCID 67063732, compound2×

Product 1

HCID 67064746HCID 67064746, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

As crude product mixture of (S)—N-(7-(3-aminopiperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (Compound 305, Example 319), trifluoroacetate salt (50 mg, 0.054 mmol) was dissolved in pyridine (2 ml). At 0° C. acetyl chloride (0.013 ml, 0.18 mmol) was added and the mixture was stirred for 2 hours at room temperature. Afterwards an additional amount of acetyl chloride (0.008 ml) was added to drive the reaction to completion. Water (2 ml) was then added to quench the reaction. The mixture was concentrated in vacuo, and the crude product was purified by preparatory HPLC (25-60% MeCN/H2O gradient+0.01% TFA). Lyophilization of the collected fractions gave the titled compound (50 mg, 33%) as a white powder. 1H NMR (400 MHz, DMSO-d6) δ=10.91 (s, 1H), 8.09 (d, J=2.3 Hz, 1H), 8.03-7.95 (m, 3H), 7.64-7.57 (m, 2H), 7.38 (s, 1H), 6.36 (d, J=2.3 Hz, 1H), 4.13 (br. s., 2H), 3.87 (br. s., 1H), 3.22-3.13 (m, 1H), 3.08 (dd, J=9.5, 11.5 Hz, 1H), 2.00-1.86 (m, 2H), 1.82 (s, 2H), 1.76 (br. s., 1H), 1.52 (br. s., 1H), 1.46 (s, 5H); ESI-MS: m/z 437.5 (M+H)+.

Workup

  1. customthe reaction to completion
  2. customto quench
  3. customthe reaction
  4. concentrationThe mixture was concentrated in vacuo
  5. customthe crude product was purified by preparatory HPLC (25-60% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-0b9db3b94c8048e4a19100b89365b436
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

Loading…