Reaction SMILES: C(O)CCCC.[ClH:7].[OH:8][CH2:9][CH2:10][N:11]([CH3:31])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([NH:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][CH:23]=1)=[O:20].C(=O)([O-])[O-].[K+].[K+].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.Cl.[NH2:62][CH2:63][C:64]1[C:69]([CH2:70][CH3:71])=[N:68][C:67]2[N:72]([CH2:75][CH3:76])[N:73]=[CH:74][C:66]=2[C:65]=1[NH:77][CH:78]1[CH2:83][CH2:82][O:81][CH2:80][CH2:79]1.Cl>O>[ClH:7].[CH2:75]([N:72]1[C:67]2=[N:68][C:69]([CH2:70][CH3:71])=[C:64]([CH2:63][NH:62][C:26](=[O:28])[C:25]3[CH:24]=[CH:23][C:22]([NH:21][C:19](=[O:20])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][N:11]([CH2:10][CH2:9][OH:8])[CH3:31])=[CH:30][CH:29]=3)[C:65]([NH:77][CH:78]3[CH2:79][CH2:80][O:81][CH2:82][CH2:83]3)=[C:66]2[CH:74]=[N:73]1)[CH3:76]
Reactant: CN(CCO)CCCCCCCC(=O)Nc1ccc(C(=O)O)cc1
Reactant: CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CN
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: O
Solvent: CCCCCO
Product: CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1ccc(NC(=O)CCCCCCCN(C)CCO)cc1
Temperature: 20 °C
Reaction time: 0.17 h

Procedure:
To stirred n-pentanol (pentan-1-ol, 15 vol, 105 L) in a glass-lined reactor at 18° C. under nitrogen is added 4-({8-[(2-hydroxyethyl)(methyl)amino]octanoyl}amino)benzoic acid hydrogen chloride (0.95 wt, 6.65 kg) (e.g. which can be as prepared in Intermediate 39A, or which can be specially ordered from Sigma-Aldrich) and potassium carbonate [325 mesh particle size (quite a fine particle size), 1.02 wt, 7.14 kg]. After stirring at 90 rpm for 10 minutes at 20±5° C., 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (0.87 wt, 6.09 kg), 1-hydroxybenzotriazole hydrate (HOBT.H2O) (0.19 wt, 1.33 kg) and 5-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine monohydrochloride (1 wt, 7.0 kg) (e.g. which is preferably substantially as prepared in Intermediate 7A) are added sequentially. The heterogeneous reaction mixture is warmed to 20±5° C., and is stirred at 90-160 rpm under nitrogen at 20±5° C. for 9 hours 20 minutes (90 minutes at 90 rpm, 90 minutes at 125 rpm, and 6 hours 20 minutes at 160 rpm). Water (10 vol, 70 L) is added and the mixture is stirred for 16 minutes while maintaining the current batch temperature; the layers are allowed to settle for 15 minutes and separated. To the upper organic layer is added 32% w/w aqueous sodium hydroxide solution (2.5 wt, 17.5 kg) over a period of 37 minutes, while maintaining the reactor contents at 20±5° C. The mixture is then heated to 45±5° C. and stirred at 75 rpm at 45±5° C. for 2 hours. The mixture is cooled to 20±5° C. and water (8 vol, 56 L) is added. The mixture is stirred for 15 minutes and allowed to settle for 15 minutes. The lower aqueous layer is removed and the remaining organic layer is held overnight without stirring. 6.5% w/w aqueous sodium chloride solution (10.4 wt, 72.8 kg) is added to the organic layer. Aqueous hydrochloric acid (17% w/w) is added over 83 minutes, while maintaining the reactor contents at 20±5° C., with the amount of 17% w/w hydrochloric acid used (e.g. about 7.0 kg to about 19.20 kg) being such as to ensure that the pH is adjusted finally to 5.75±0.25, with a final pH of less than 5.5 being avoided to minimise loss of the product (as hydrochloride) to the aqueous layer. The mixture is stirred for 30 minutes and allowed to settle for 30 minutes. The organic layer is separated, is stirred with 4% aqueous sodium hydroxide solution (10.4 wt, 72.8 kg) for 15 minutes while maintaining the current batch temperature, and is allowed to settle for 30 minutes. The lower aqueous layer is removed. Water (10 vol, 70 L) is added to the organic layer and stirred for at least 15 minutes while maintaining the current batch temperature. The agitator is then switched off. The reactor contents are heated to 25±5° C., allowed to settle for 30 minutes and then cooled to 20±5° C. The lower aqueous layer is removed. The organic layer is transferred from the reactor, the reactor is washed with n-pentanol (pentan-1-ol, 2 vol, 14 L), and the combined organic mixture is filtered to remove any insoluble matters while being returned to the reactor. The organic mixture is allowed to settle for about 1 hour, after which a lower aqueous layer forms which is removed. The separated organic layer is allowed to settle overnight, after which a lower aqueous layer forms which is removed. A solution yield is obtained on the organic solution using a calibrated HPLC system and 4.49M aqueous hydrochloric acid (1 equivalent, 3.80 kg) is added, maintaining the reactor contents at 20 ±5° C. The mixture is concentrated in vacuo to 10 volumes (70 L), by vacuum distillation at about −0.901 to −0.912 barg, at internal temperatures starting from 46.5° C. and rising to about 78° C. (jacket temperature 60° C., rising to 90° C., and rising again to 100° C.). The mixture is then adjusted to 85±5° C. under an atmospheric pressure of nitrogen. A slurry of seed crystals (0.007 kg, 0.001 wt) of N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-4-({8-[(2-hydroxyethyl)(methyl)amino]octanoyl}amino)benzamide monohydrochloride (preferably the Form 1 anhydrate thereof) in n-pentanol (pentan-1-ol, 0.07 L, 0.01 vol) is added. The mixture is cooled to 60±5° C., stirred for 2 hours at 60±5° C., and then adjusted to 55±5° C. Tert-butyl methyl ether (TBME) (4.3 vol, 30.1 L) is added over 5 minutes, maintaining the reactor contents at 50±5° C. The resultant mixture is cooled to 20±5° C. over about 1 hour, and then is stirred for about 14 hours at 20±5° C. The resultant slurry is filtered under 0.5 to 1 barg of nitrogen pressure using a 20 micron filter cloth. The reactor and then the filter cake is washed with n-pentanol (pentan-1-ol, 2.5 vol, 17.5 L), and the filter cake is then washed with TBME (2.5 vol, 17.5 L), the filter cake washes being under 0.5 to 1 barg of nitrogen pressure. Residual solvent in the filter cake is removed under nitrogen pressure. Then the filtered solid is dried at 55±5° C. in vacuo in a vacuum tray dryer under a bleed of 5 L/min nitrogen until the product achieves a constant temperature for at least 4 hours, and then is cooled to <30° C., to yield the desired product N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-4-({8-[(2-hydroxyethyl)(methyl)amino]octanoyl}amino)benzamide monohydrochloride.