2-(methylamino)acetic acid;hydrochloride

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: When the product of Step C and azatadine 3 methylcarboxylate hydrochloride were substituted for 4-(5-(((4-fluorophenyl))isopropyl)amino)methyl)thiophen-2-yl)benzaldehyde and sarcosine hydrochloride, respectively, in Example 22, Step C, the similar procedure afforded the title compound in 48% yield, as pale paste. 1H-NMR (CDCl3) 9.32 (s, 1H); 8.53 (s, 1H); 8.12-8.07 (m, 2H); 8.00 (dd, 1H, J=8.7, 2.4 Hz); 7.91 (t, 1H, J=5.55 Hz); 7.7-7.6 (m, 4H); 7.38 (d, 2H, J=8.22 Hz); 3.71 (s, 3H); 3.67 (s, 2H); 3.57-3.53 (m, 2H); 3.39-3.35 (m, 3H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: When the product of Step C and azatadine 3 methylcarboxylate hydrochloride were substituted for 4-(5-(((4-fluorophenyl))isopropyl)amino)methyl)thiophen-2-yl)benzaldehyde and sarcosine hydrochloride, respectively, in Example 22, Step C, the similar procedure afforded the title compound in 48% yield, as pale paste. 1H-NMR (CDCl3) 9.32 (s, 1H); 8.53 (s, 1H); 8.12-8.07 (m, 2H); 8.00 (dd, 1H, J=8.7, 2.4 Hz); 7.91 (t, 1H, J=5.55 Hz); 7.7-7.6 (m, 4H); 7.38 (d, 2H, J=8.22 Hz); 3.71 (s, 3H); 3.67 (s, 2H); 3.57-3.53 (m, 2H); 3.39-3.35 (m, 3H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: When the product of Step A and azatadine 3 methylcarboxylate hydrochloride were substituted for 4-(5-(((4-fluorophenyl))-isopropyl)amino)methyl)thiophen-2-yl)benzaldehyde and sarcosine hydrochloride, respectively, in Example 22, Step C, the similar procedure afforded the title compound in 76% yield, as light yellow paste. 1H-NMR (CDCl3) 7.17 (d, 2H, J=8.56 Hz); 6.81 (d, 2H, J=8.61 Hz); 3.91 (t, 2H, J=1.98 Hz); 3.71-3.65 (m, 7H); 3.44-3.41 (m, 3H); 2.03-1.17 (m, 10H); 1.17 (s, 3H); 1.01 (s, 3H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: When the product of Step B and azatadine 3 methylcarboxylate hydrochloride were substituted for 4-(5-(((4-fluorophenyl))-isopropyl)amino)methyl)thiophen-2-yl)benzaldehyde and sarcosine hydrochloride, respectively, in Example 22, Step C, the similar procedure afforded the title compound in 69% yield, as a pale paste. 1H-NMR (CDCl3) 7.24-7.20 (m, 2H); 7.16 (d, 2H, J=8.55 Hz); 6.91 (d, 2H, J=8.62 Hz); 6.85 (d, 1H, J=8.17 Hz); 4.92 (s, 2H); 3.82 (s, 3H); 3.69 (s, 3H); 3.52 (s, 2H); 3.49 (s, 1H); 3.47 (s, 2H); 3.31-3.24 (m, 3H); 2.08 (s, 6H); 2.04 (s, 3H); 1.75 (s, 6H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: When the product of Step C and azatadine 3 methylcarboxylate hydrochloride were substituted for -(5-(((4-fluorophenyl))isopropyl)amino)methyl)thiophen-2-yl)benzaldehyde and sarcosine hydrochloride, respectively, as in Example 22, Step C, the similar procedure afforded the title compound in 31% yield, as light green paste. 1H-NMR (CDCl3) 8.43 (d, 1H, J=2.29 Hz); 7.96-7.91 (m, 3H); 7.63 (d, 3H); 7.54-7.39 (m, 3H); 7.38 (d, 2H, J=8.18 Hz); 6.85 (s, 1H); 3.73 (s, 3H); 3.71 (s, 2H); 3.71-3.62 (broad, 2H); 3.42-3.35 (b, 3H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: When the product of Step C and azatadine 3 methylcarboxylate hydrochloride were substituted for -(5-(((4-fluorophenyl))isopropyl)amino)methyl)thiophen-2-yl)benzaldehyde and sarcosine hydrochloride, respectively, as in Example 22, Step C, the similar procedure afforded the title compound in 31% yield, as light green paste. 1H-NMR (CDCl3) 8.43 (d, 1H, J=2.29 Hz); 7.96-7.91 (m, 3H); 7.63 (d, 3H); 7.54-7.39 (m, 3H); 7.38 (d, 2H, J=8.18 Hz); 6.85 (s, 1H); 3.73 (s, 3H); 3.71 (s, 2H); 3.71-3.62 (broad, 2H); 3.42-3.35 (b, 3H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: When the product of Step D and azatadine 3 methylcarboxylate hydrochloride were substituted for 4-(5-(((4-fluorophenyl)) isopropyl)amino)methyl)thiophen-2-yl)benzaldehyde and sarcosine hydrochloride, respectively, in Example 22, Step C, the similar procedure afforded the title compound in 58% yield, as a pale paste. 1H-NMR (CDCl3) 8.04 (d, 2H, J=8.4 Hz); 7.78-7.51 (m, 8H); 7.4 (d, 2H, J=8.2 Hz); 7.16 (d, 1H, J=1.21 Hz); 3.76 (s, 2H); 3.7 (s, 3H); 3.73-3.62 (m, 4H); 3.47-3.41 (m, 3H); 2.58 (bs, 3H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: When the product of Step B and azatadine 3 methylcarboxylate hydrochloride were substituted for 4-(5-(((4-fluorophenyl)) isopropyl)amino)methyl)thiophen-2-yl)benzaldehyde and sarcosine hydrochloride, respectively, in Example 22, Step-C, the similar process afforded the title compound in 66% yield, as pale paste. 1H-NMR (CDCl3) 7.49 (d, 2H, J=8.28 Hz); 7.30 (d, 2H, J=8.29 Hz); 7.22 (s, 2H), 7.06 (s, 1H); 3.90 (s, 9H); 3.68 (s, 3H); 3.64 (s, 2H); 3.56-3.52 (m, 2H); 3.37-3.32 (m, 3H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: When the product of Step A and 4-bromobenzaldehyde were substituted for sarcosine hydrochloride salt and 4-(5-(((4-fluorophenyl)) isopropyl)amino)methyl)thiophen-2-yl)benzaldehyde, respectively, in Example 22, Step C, the similar process afforded the title compound in 93% yield, as a pale paste. 1H-NMR (CDCl3) 7.39 (d, 2H, J=8.18 Hz); 7.14 (d, 2H, J=8.08 Hz); 6.91-6.81 (m, 2H); 6.62-6.57 (m, 2H); 4.26 (s, 2H); 4.11-4.04 (m, 1H); 1.18 (d, 2H, J=5.34 Hz).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: When the product of Step A and 4-bromobenzaldehyde were substituted for sarcosine hydrochloride salt and 4-(5-(((4-fluorophenyl)) isopropyl)amino)methyl)thiophen-2-yl)benzaldehyde, respectively, in Example 22, Step C, the similar process afforded the title compound in 93% yield, as a pale paste. 1H-NMR (CDCl3) 7.39 (d, 2H, J=8.18 Hz); 7.14 (d, 2H, J=8.08 Hz); 6.91-6.81 (m, 2H); 6.62-6.57 (m, 2H); 4.26 (s, 2H); 4.11-4.04 (m, 1H); 1.18 (d, 2H, J=5.34 Hz).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: When the product of Step C and azatadine 3 methylcarboxylate hydrochloride were substituted for 4-(5-(((4-fluorophenyl)(isopropyl)amino)methyl)thiophen-2-yl)benzaldehyde and sarcosine hydrochloride, respectively, in Example 22, Step C, the similar process the title compound in 69% yield, as pale paste. 1H-NMR (CDCl3) 7.64 (d, 2H, J=8.8 Hz); 7.58 (d, 2H, J=8 Hz); 7.54 (d, 2H, J=8.15 Hz); 7.36 (d, 2H, J=8.12 Hz); 7.17 (t, 1H, J=8.14 Hz); 6.80 (dd, 1H, J=8.07, 2.21 Hz); 6.72 (t, 1H, J=2.10 Hz); 6.64 (dd, 1H, J=7.80, 1.67 Hz); 3.74 (s, 3H); 3.71 (s, 2H); 3.69 (s, 3H); 3.64-3.58 (m, 2H); 3.42-3.36 (m, 4H); 3.18 (s, 3H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: When the product of Step C and 2,2-dimethyl-1,3-dioxan-5-amine were substituted for 4-(5-(((4-fluorophenyl)(isopropyl)amino)methyl)-thiophen-2-yl)benzaldehyde and sarcosine hydrochloride in Example 22, Step C, the similar process afforded the title compound in 48% yield, as creamy paste. 1H-NMR (CDCl3) 7.24 (d, 2H, J=7.92 Hz), 7.11 (d, 2H, J=7.92 Hz), 6.87 (t, 2H, J=8.9 Hz), 6.69-6.62 (m, 2H), 3.95 (dd, 2H, J=11.7, 3.6 Hz), 3.83-3.69 (m, 4H), 3.06 (t, 2H, J=7.54 Hz), 2.66-2.58 (m, 3H), 1.83-1.76 (m, 3H), 1.41 (s, 3H), 1.4 (s, 3H), 1.08 (d, 2H, J=6.59 Hz).