Water → HCID 67064467, compound

HRID 1409240Notes

Reaction equation

HRID 1409240 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 67063950HCID 67063950, compound2×

Product 1

HCID 67064467HCID 67064467, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

As crude product mixture of (R)—N-(7-(3-aminopiperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (Compound 309 in Example 323) and trifluoroacetate salt (65 mg, 0.165 mmol) was dissolved in pyridine (2 ml). At 0° C. acetyl chloride (0.025 ml, 0.353 mmol) was added and the mixture was stirred for 2 hours at room temperature. Afterwards an additional amount of acetyl chloride (0.009 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 (35 mg, 34% yield). 1H NMR (400 MHz, DMSO-d6) δ=10.90 (s, 1H), 8.08 (d, J=2.3 Hz, 1H), 8.03-7.94 (m, 4H), 7.64-7.56 (m, 2H), 7.36 (s, 1H), 6.35 (d, J=2.3 Hz, 1H), 4.26-4.17 (m, 1H), 4.13 (d, J=11.9 Hz, 1H), 3.86 (br. s., 1H), 3.14 (s, 1H), 3.07 (dd, J=9.5, 11.7 Hz, 1H), 1.90 (br. s., 2H), 1.81 (s, 3H), 1.75 (br. s., 1H), 1.59-1.47 (m, 1H), 1.45 (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-132ed9fe24ca40ce92556d42c76a5ecd
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

Loading…