2
40 J . Org. Chem., Vol. 67, No. 1, 2002
Cuperly et al.
Ma ter ia ls a n d Solven ts. All reagents were commercially
m/z 202 (97), 201 (68), 100 (100), 199 (100), 199 (62), 121 (27),
available and were purified by distillation when necessary.
BuLi was used as 1.6 M solutions in hexanes. 2-(dimethylami-
no)ethanol was distilled and stored over molecular sieves
before use. Hexane, THF, and xylene were distilled and stored
on sodium wire before use.
7 9 2
79 (10). Anal. Calcd for C H N Br: C, 41.82; H,4.51; N,13.93.
Found: C, 41.90; H, 4.48; N, 13.83.
2-Iod o-4-p yr id yl(d im eth yl)a m in e (2g). Column chroma-
tography (AcOEt) yielded 2g (903 mg, 81%) as a white solid:
1
mp 67-69 °C; H NMR δ 2.97 (s, 6H), 6.45 (dd, J ) 5.9 and
H
Gen er a l P r oced u r e for C-2 F u n ction a liza tion of 4-D-
MAP (1). A solution of 2-(dimethylamino)ethanol (0.8 mL, 8
mmol) in hexane (10 mL) was cooled at ca. -5 °C, and BuLi
2.0 Hz, 1H), 6.88 (d, J ) 2.0 Hz, 1H), 7.89 (d, J ) 5.9 Hz, 1H);
C NMR δ 39.1, 106.5, 116.4, 119.25, 149.5, 154.8; MS (EI)
C
1
3
+
m/z 248 (M , 100), 121 (76), 106 (15). Anal. Calcd for
I: C, 33.89; H, 3.66; N, 11.29. Found: C, 34.03; H, 3.63;
N, 11.16.
Dim eth yl(2-tr ibu tylsta n n yl-4-p yr id yl)a m in e (2h ). Col-
umn chromatography (70/30 Et N, AcOEt) yielded 2g (1.15 g,
70%) as an oil: 1H NMR δ
0.85 (t, J ) 8.0 Hz, 9H), 1.15 (t, J
(10 mL, 16 mmol) was added dropwise under a nitrogen
7 9 2
C H N
atmosphere. After 30 min at 0 °C, 4-DMAP (488 mg; 4 mmol)
was added at once as a solid. After 1 h of stirring at 0 °C, the
reaction medium was cooled at -78 °C, and a solution of the
appropriate electrophile (10 mmol) in hexane (20 mL) was
added dropwise (20 min). The temperature was then allowed
to raise to 0 °C (1.5 h). Hydrolysis was performed at this
3
H
) 8.0 Hz, 6H), 1.3 (m, 6H), 1.55 (m, 6H), 2.98 (s, 6H), 6.37
(dd, J ) 5.9 and 3.0 Hz, 1H), 6.65 (d, J ) 3.0 Hz, 1H), 8.34 (d,
J ) 5.9 Hz, 1H); 13C NMR δ
9.4, 13.7, 27.1, 29.2, 38.7, 105.4,
Sn: C, 55.50;
temperature with H
extracted with diethyl ether (20 mL) and then with dichlo-
romethane (20 mL). After drying (MgSO ), filtration, and
2
O (20 mL). The aqueous phase was first
C
115.4, 150.0, 152.1, 172. Anal. Calcd for C19
36 2
H N
4
H, 8.82; N, 6.81. Found: C, 55.65; H, 8.71; N, 6.78.
evaporation of solvents, the crude product was purified by
column chromatography.
Gen er a l P r oced u r e for Stille Cr oss-Cou p lin g of Sta n -
n a n e 2h . To a solution of 2h (615 mg; 1.5 mmol) in xylene
Dim eth yl(2-m eth ylsu lfa n yl-4-p yr id yl)a m in e (2a ). Col-
(30 mL) under nitrogen atmosphere were added PdCl
2 3 2
(PPh )
umn chromatography (AcOEt) yielded 2a (645 mg, 96%) as a
(53.4 mg; 0.0745 mmol) and PPh (39.5 mg; 0.149 mmol) and
3
1
the appropriate heteroaromatic halide (generally 1.6 mmol
except for 2,6-dibromopyridine (3 mmol was added)). The
reaction medium was then refluxed for 12 h. After being cooled
at room temperature, the black mixture was filtered over a
pad of Celite and the xylene phase was extracted three times
with aqueous HCl (25%). The aqueous phase was then made
yellow oil: H NMR δ
H
2.55 (s, 3H), 2.95 (s, 6H), 6.30 (dd, J )
6
.1 and 2.5 Hz, 1H), 6.40 (d, J ) 2.5 Hz, 1H), 8.1 (d, J ) 6.1
13
Hz, 1H); C NMR δ
C
13.3, 39.0, 102.9, 103.9, 149.0, 154.1,
+
1
1
59.5; MS (EI) m/z 168 (M , 99), 167 (59), 153 (22), 122 (100),
8 12 2
21 (49), 107 (39), 79 (32). Anal. Calcd for C H N S: C, 57.11;
H, 7.19; N, 16.65. Found: C, 57.40; H, 7.16; N, 16.26.
basic by the addition of NH
extracted thrice with dichloromethane (20 mL). After drying
(MgSO ), filtration, and evaporation of solvent, the crude
4
OH (10% and subsequently
N,N-Dim eth yl-3,5-d i(m eth ylsu lfa n yl)a n ilin e (3). Col-
umn chromatography (60/40 hexanes, AcOEt) yielded 3 (137
1
4
mg, 16%) as a yellow oil: H NMR δ
H
2.57 (s, 6H), 2.95 (s,
13.2, 39.1, 100.2, 154.3, 158.5;
MS (EI) m/z 214 (M , 100), 213 (41), 168 (54), 135 (50), 107
46), 80 (54). Anal. Calcd for C : C, 50.43; H, 6.58; N,
3.07. Found: C, 50.56; H, 6.78; N, 12.85.
-2H-4-P yr id yl(d im eth yl)a m in e (2b). Recrystallization
from hexanes yielded 2b as a mixture with 1 (344 mg, 71%,
1
3
product was purified by column chromatography or precipita-
tion in diethyl ether.
Dim eth yl[2-(2-p yr id yl)-4-p yr id yl]a m in e (5a ). Column
6
H), 6.19 (s, 2H); C NMR δ
C
+
(
1
9 14 2 2
H N S
3
chromatography (70/30 Et N, AcOEt) yielded 5a (215 mg, 72%)
1
as white solid: mp 96-98 °C; H NMR δ
H
3.1 (s, 6H), 6.53
2
(
dd, J ) 5.9, 2.7 Hz, 1H), 7.28 (m, 1H), 7.7 (d, J ) 2.7 Hz, 1H),
7
.8 (dt, J ) 7.8, 1.7 Hz, 1H), 8.32 (d, J ) 5.9 Hz, 1H), 8.37 (d,
13
1
%
6
1
D >95): H NMR δ
H
3.02 (s, 6H), 6.51 (m, 2H), 8.24 (d, J )
38.9, 106.2, 106.6, 149.0, 149.2, 149.3,
49.6, 154.1; MS (EI) m/z 123 (M , 83), 122 (100), 93 (2), 79
J ) 8.0 Hz, 1H), 8.67 (dd, J ) 4.7, 0.8 Hz, 1H); C NMR δ
C
1
3
.7 Hz, 1H); C NMR δ
C
3
1
1
9.1, 103.8, 106.6, 121.25, 123.3, 136.7, 148.8, 149.3, 155.2,
+
+
56.1, 156.9; MS (EI) m/z 199 (M , 53), 184 (100), 156 (48),
55 (19), 78 (22). Anal. Calcd for C12 : C, 72.34; H, 6.58;
(
11).
-(Dim et h yla m in o)-2-p yr id ylp h en ylm et h a n on e (2c).
Column chromatography (AcOEt) yielded 2c (588 mg, 65%)
13 3
H N
4
N, 21.09. Found: C, 72.46; H, 6.41; N, 21.34.
Dim eth yl[2-(2-p yr a zin yl)-4-p yr id yl]a m in e (5b). Column
1
as a white solid: mp 68-71 °C; H NMR δ
H
3.1 (s, 6H), 6.62
chromatography (70/30 Et
3
N, AcOEt) yielded 5b (255 mg, 85%)
(
m,1H), 7.25 (m, 1H), 7.45 (t, J ) 7.4 Hz, 2H), 7.55 (t, J ) 7.1
1
as an orange solid: mp100-102 °C; H NMR δ
H
3.1 (s, 6H),
.55 (dd, J ) 5.9, 2.7 Hz, 1H), 7.60 (d, J ) 2.7 Hz, 1H), 8.34
1
3
Hz, 1H); 8.05 (d, J ) 7.6 Hz, 2H); 8.31 (d, J ) 5.7 Hz, 1H);
NMR δ 39.2, 107.3, 108.3, 128.0, 130.9, 132.6, 136.8, 148.7,
54.9, 155.4, 186.5; MS (EI) m/z 226 (M , 100), 225 (99), 197
49), 183 (69), 105 (53), 77 (79). Anal. Calcd for C14 O:
C, 74.31; H, 6.24; N, 12.38. Found: C, 74.45; H, 6.15; N, 12.47.
-Diph en ylph osph a n yl-4-pyr idyl(dim eth yl)a m in e (2d ).
Column chromatography (AcOEt) yielded 2d (1.1 g, 90%) as a
C
6
C
13
(d, J ) 5.9 Hz, 1H), 8.57 (m, 2H), 9.60 (d, J ) 1.5 Hz, 1H); C
+
1
(
C
NMR δ 39.1, 104.1, 107.1, 143.1, 143.4, 144.0, 149.5, 151.8,
53.9, 155.0; MS (EI) m/z 200 (M , 88), 185 (100), 157 (44),
58 (24), 79 (8). Anal. Calcd for C11
H
14
N
2
+
1
1
12 4
H N : C, 65.98; H, 6.04;
2
N, 27.98. Found: C, 66.05; H, 6.24; N, 27.67.
N,N-Dim et h yl-2-(4-(d im et h yla m in o)-2-p yr id yl)-4-p y-
r id in a m in e (5c). Precipitation from diethyl ether yielded 5c
1
yellow viscous oil: H NMR δ
H
2.76 (s, 6H), 6.32 (m,2H), 7.29
(
m, 6H), 7.42 (m, 4H); 8.31 (d, J ) 5.7 Hz, 1H); 13C NMR δ
C
1
(
3
218 mg, 60%) as a brown solid: mp 230-232 °C; H NMR δ
H
3
1
6
8.4, 104.9, 111.1, 128.10, 128.4, 133.7, 136.6, 149.8, 153.5,
.1 (s, 12H), 6.50 (dd, J ) 5.9, 2.9 Hz, 2H), 7.49 (d, J ) 2.9
3
1
+
62.3; P NMR δ
4), 305 (100), 229 (9), 228 (17), 121 (1). Anal. Calcd for
P: C, 74.49; H, 6.25; N, 9.14. Found: C, 74.53; H,
.08; N, 9.38.
-Ch lor o-4-p yr id yl(d im eth yl)a m in e (2e). Column chro-
matography (AcOEt) yielded 2e (562 mg, 90%) as a white
P
-2.01 ppm; MS (EI) m/z 307 (12), 306 (M ,
13
C
Hz, 2H), 8.30 (d, J ) 5.9 Hz, 2H); C NMR δ 39.3, 104.0,
+
1
1
6
06.4, 149.1, 155.2, 156.9; MS (EI) m/z 242 (M , 9), 227 (42),
99 (23), 121 (40), 120 (100). Anal. Calcd for C14 : C,
19 19 2
C H N
18 4
H N
6
9.39; H, 7.49; N, 23.12. Found: C, 69.48; H, 7.31; N, 22.96.
2
2-(6-Br om o-2-p yr id yl)-4-p yr id yl(d im eth yl)a m in e (5d ).
Column chromatography (70/30 Et N, AcOEt) yielded 5d (380
3
1
mg, 91%) as an orange oil: 1H NMR δH 3.05 (s, 6H), 6.49 (dd,
solid: mp 80-82 °C; H NMR δ
H
3.00 (s, 6H), 6.40 (dd, J )
6
.1 and 2.3 Hz, 1H), 6.47 (d, J ) 2.3 Hz, 1H), 7.97 (d, J ) 6.1
J ) 6.0, 2.7 Hz, 1H), 7.42 (d, J ) 7.8 Hz, 1H), 7.60 (m, 2H),
1
3
13
Hz, 1H); C NMR δ
MS (EI) m/z 158 (23), 157 (37), 156 (72), 155 (100), 121 (4).
Anal. Calcd for C Cl: C, 53.66; H, 5.79; N, 17.89. Found:
C, 53.75; H, 5.80; N, 17.59.
-Br om o-4-p yr id yl(d im eth yl)a m in e (2f). Column chro-
matography (AcOEt) yielded 2f (756 mg, 86%) as a brown
C
39.2, 105.4, 105.8, 149.0, 152.2, 156.0;
8.26 (d, J ) 6 Hz, 1H), 8.34 (d, J ) 7.8 Hz, 1H); C NMR δ
C
39.1, 104.1, 106.9, 119.8, 127.4, 138.7, 141.1, 149.4, 154.3,
155.0, 158.2; MS (EI) m/z 279 (69), 278 70), 264 (99), 262 (100),
236 (42), 234 (43), 198 (17), 155 (24), 77 (9). Anal. Calcd for
7
9 2
H N
2
12 3
C H12BrN : C, 51.82; H, 4.34; N, 15.11. Found: C, 52.11; H,
4.46; N, 14.98.
N,N-Dim eth yl-2-[6-(4-(d im eth yla m in o)-2-p yr id yl)-2-p y-
r id yl]-4-p yr id in a m in e (5e). Precipitation from diethyl ether
yielded 5e (230 mg, 50%) as a brown solid: mp > 300 °C dec;
1
gummy solid: H NMR δ
H
3.00 (s, 6H), 6.43 (dd, J ) 5.9 and
2
.1 Hz, 1H), 6.63 (d, J ) 2.1 Hz, 1H), 7.93 (d, J ) 5.9 Hz, 1H);
1
3
C
C NMR δ 39.2, 106.2, 109.2, 143.1, 149.3, 155.7; MS (EI)